Irf4 Cancer



"These proof-of-principle studies will enable rapid clinical development of anti-sense oligonucleotide-mediated IRF4 inhibition to prevent myeloma relapse driven by drug-resistant cancer stem cells," said co-senior author Catriona Jamieson, MD, PhD, Koman Family Presidential Endowed Chair in Cancer Research, deputy director of Moores Cancer. [PMID 21270109] A germline variant in the interferon regulatory factor 4 gene as a novel skin cancer risk locus. The emergence of a common progenitor cell has been postulated for the association of CD30-positive lymphoproliferative disease (LPD) and mycosis fungoides (MF) within the same patient. Mouse (93%), Rat (92%). 2016 Jul;6(7):714-26. IRF4 is widely expressed in leucocytes and is essential for the development, activation, differentiation, and/or apoptosis of T helper (Th) cell subsets including Th2, Th9, Th17, T follicular helper (Tfh) cells, or T (Treg) cells. To determine molecular switches directing induction of LC immune activation, we performed mathematical modelling of gene regulatory networks identified by single cell RNA sequencing of LCs exposed to TNF-alpha, a key pro-inflammatory. Early CRC detection is key and is associated with improved survival outcomes. Immunohistochemistry-Paraffin: IRF4 Antibody [NBP1-82814] - Staining of human kidney shows no postivity in cells in tubules as expected. We examined the prognostic significance of IRF4 mRNA expression in node-negative breast cancer. Large B-cell lymphoma with IRF4 rearrangement is a recently described, low-grade entity that occurs most commonly in children and young adults. IRF4 expression defines intratumoral Treg heterogeneity. IRF4 instructs effector Treg differentiation and immune suppression in human cancer. This adaptive process is triggered by the specific recognition of cancer cells by T cells, which leads to the production of immune-activating cytokines. Systemic IRF4 deficiency accelerates PDAC tumor growth and expands MDSC in vivo. MUM1) genes by Fluorescence in situ Hybridization (FISH). DF6198 at 1/100 staining Human ovarian cancer and adjacent normal tissues by IHC-P. David Baltimore's lab contains the insert Mouse IRF4 and is published in Blood. Furthermore, Th2-preferential in vivo binding of NFAT1 and IRF4 to the CNS-9 region was observed by ChIP. They provide nurturing signals to multiple myeloma cells and promote immune escape. A chromosomal translocation involving this gene and the IgH locus, t(6;14)(p25;q32), may be a cause of multiple myeloma. T4SS-dependent TLR5 activation by Helicobacter pylori infection. The test analyzes 324 genes as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) and is a companion diagnostic to. IRF4 also enhances DNA binding by the E2A-encoded gene product E47 and functions synergistically to activate transcription from the Igκ 3′ enhancer. Cancer Panel v2; these genes are indicated in dark grey cells. IRF4 is a member of the IRF family of transcription factors, expressed in most cell types of the immune system. Studies have shown a connection between the synthesis of proteins, known as IRF4, and low patient survival rates. This would suggest that this mirror repeat sequence, which allows for strong induction by IRF4, is a binding site for IRF4 in the interferon β promoter. 100% Guaranteed. invasive cervical cancer for up to 15·5 years compared with women with normal cytology, according to new research. IRF4 protein expression showed a positive change with overexpression or silencing of the MBD2 gene, whereas there was. Immunohistochemistry-Paraffin: IRF4 Antibody [NBP1-82814] - Staining of human tonsil shows strong nuclear positivity in non-germinal center. Figure 7 a-b display the immunohistochemical images of IRF4 in normal tissues and cervical cancer tissues based on the HPA database. Western blot analysis was performed using IRF4 / MUM1 antibody (GTX129135) diluted at 1:500. Modified dose intensive R- CODOX-M/IVAC for HIV-associated burkitt (BL) (AMC 048) shows efficacy and tolerability, and predictive potential of IRF4/MUM1 expression. The 55-year history of the drug thalidomide is Shakespearean in scope, awash in unintended consequences, tragedy, resilience, driven characters, and redemption. Funding period: 2019 - 2022. "Prognostic significance of interferon regulating factor 4 (IRF4) in node-negative breast cancer. Therapeutic targeting of IRF4 to treat multiple myeloma. Gene of 19,4 kb with 9 exons and 8 introns. IRF4 is not prognostic in stomach cancer. Past studies have shown that high IRF4 levels are associated with lower overall survival rates for patients with the disease. NeoGenomics is a premier cancer diagnostics and pharma services company offering innovative diagnostic, prognostic and predictive testing. This plasmid is available through Addgene. Ighg1 tm1(cre)Cgn /Ighg1 + Irf4 tm1Rdf /Irf4 tm1. Mouse insertional mutagenesis experiments support the designation of IRF4 as a cancer causing gene. 6a and Supplementary. However, the biological role of IRF4 in colon cancer is still unclear. Gene rearrangements involving the DUSP22-IRF4 gene region have been reported in CD30-positive, ALK-negative anaplastic large cell lymphoma and are associated with a favorable clinical outcome. Association of IRF4 SNP rs12203592 with melanoma-specific survival. progression of cervical cancer by targeting miR-1228-3p/IRF4 Axis Zhi-Min Deng1†, Fang-Fang Dai1†, Quan Zhou2* and Yan-Xiang Cheng1* Abstract Background: With the broadened application of gene expression profiles analysis, the role of miRNA and circRNA are of increasing concern in recent years, especially during the pathogenesis of cancer. Fusions, missense mutations, nonsense mutations, and silent mutations are observed in cancers such as hematopoietic and lymphoid cancers, intestinal cancer, and ovarian cancer. Rearrangement has been reported in a subset of patients with lymphomatoid papulosis (LyP). 2016 Jul;6(7):714-26. In this study, we used a genetic approach to determine. Plus, IRF4 is involved in various inflammatory responses to microbial pathogens such as muramyl dipeptide (MDP) or lipopolysaccharide (LPS). According to the National Cancer Institute, multiple myeloma is the second most common blood cancer in the United States, with more than 32,000 new cases predicted in 2020 and a five-year survival. IRF4 directly represses IRF8 and upregulates SHIP gene expression that results in stronger BCR-induced calcium. It can be seen from the legend that in normal squamous epithelial cells, the staining level of IRF4 is low, the intensity is moderate, and the quantity < 25%. One notable IRF4 target gene that was down-regulated was the gene that encodes a protein called Myc, which strongly encourages cell division and growth. "These proof-of-principle studies will enable rapid clinical development of anti-sense oligonucleotide-mediated IRF4 inhibition to prevent myeloma relapse driven by drug-resistant cancer stem cells," said co-senior author Catriona Jamieson, MD, PhD, Koman Family Presidential Endowed Chair in Cancer Research, deputy director of Moores Cancer. Study supports launch of Phase I clinical trial to test a designer DNA agent — an antisense oligonucleotide that targets a gene called IRF4 — in patients with multiple myelomaMany patients with multiple myeloma, a type of blood cancer, eventually dev. motifs can be recognized by IRF4 in conjunction with PU. Cancer Immunology, Immunotherapy (2020) 69:2101-2112 2105 1 3 IRF4 (MFI x 10 2) 10 8 6 4 2 0-+ -+ + Tumor status Isotyp e Blood Splee n Tu mo r PMN-MDSC a b Coun t Blood Spleen Tu mor. In addition, simvastatin, which suppresses IRF4 expression in MDSCs, could enhance the. , 2012; De Silva, Simonetti, Heise, & Klein, 2012; Eguchi et al. IRF4 instructs effector Treg differentiation and immune suppression in human cancer. Gene expression analysis of these genes using a data set from Pau Ni I. 2015 Jun 1; 24(11): 3296-303. IRF4 dependency in myeloma is an example of 'non-oncogene addiction', where cancer cells depend on a normal cellular protein for proliferation and/or survival. For prostate cancer, this includes abiraterone and enzalutamide. 91 x 10e-20) of all SNPs studied. 5% to 7%, in the plasma of colonoscopy-confirmed healthy subjects, with the sensitivity for detection of ctDNA in colonoscopy-confirmed patients with colorectal cancer being 65%, 54. Promoter methylation of IRF4 (p < 0. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non-small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. For an introduction to IRF4 please see my June 27 th post. : Related Articles Association of IRF4 SNP rs12203592 with melanoma-s. 1182/blood-2014-02-553842. This community is not edited and does not necessarily reflect the views of Nature Portfolio. 15th International Congress of Immunology and Allergy, 2021. EasyBlot anti-Rabbit IgG (GTX221666-01) was used as a secondary reagent. Ionis teamed up with researchers at the University of California, San Diego to inhibit the gene IRF4 in multiple myeloma using an antisense oligonucleotide. Denny JC, Bastarache L, Ritchie MD et al. , 2012; De Silva, Simonetti, Heise, & Klein, 2012; Eguchi et al. Past studies have shown that high IRF4 levels are associated with lower overall survival. Plasmid pMIG-IRF4 from Dr. It is required for immunoglobulin class switching and terminal differentiation of B cells. Genetic deletion of IRF4 was found in miR-125b-induced B-cell cancer, but its role in oncogenic miR-125b-induced B-cell transformation is still unknown. 2021 Jun 12. IRF4 and IRF8 are immune-system specific members of the IRF family of transcriptions factors that have crucial and diverse functions in regulating B and T lymphocytes as well as macrophages and dendritic cells. IRF4 dependency in MM is thus a prime example of a newly appreciated phenomenon termed ‘non-oncogene addiction’ in which cancer cells develop an exaggerated reliance upon a normal cellular protein as a result of their genetic and biological abnormalities. However, the biological role of IRF4 in colon cancer is still unclear. IRF4 also enhances DNA binding by the E2A-encoded gene product E47 and functions synergistically to activate transcription from the Igκ 3′ enhancer. dead or alive) for all individuals in the patient cohort, based on the same data that underlies the corresponding Kaplan-Meier plots. 6% and 59% respectively. Positivity for the rearrangement is a positive prognostic sign. Ariela Noy 1, Lawrence Kaplan 2, Jeannette Lee 3, Ethel Cesarman 4 & Wayne Tam 4 Infectious Agents and Cancer volume 7, Article number: O14 (2012) Cite this article. An exhausted T cell with TOX (blue) in the nucleus. dead or alive) for all individuals in the patient cohort, based on the same data that underlies the corresponding Kaplan-Meier plots. 0001), and MSC (p < 0. Interferon regulatory factor 4 (IRF4) is a transcription factor from the IRF factor family that exerts regulatory functions in the immune system and oncogenesis. IRF4 is a member of the IRF family of transcription factors, expressed in most cell types of the immune system. 0001), ELMO1 (p < 0. Jesse Boehm's lab contains the insert IRF4 and is published in Cancer Discov. 1 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. IRF4 deficiency as the pathogenic event underlying the patient's immunologic impairment is reinforced by comparison with the phenotypic characteristics of distinct Irf42/2 mouse models, which are strikingly similar to those of the patient (Table I). IRF4/DUSP22 Gene Rearrangement. Cyclosporine A treatment on wild type Th2 cells or Th2 cells derived from NFAT1 knockout (NFAT1-/-) mice showed significantly reduced trans-activity of CNS-9. Both IRF4 WT and IRF4 L116R proteins bound the DNA variants with different K D value ranging from low nanomolar to high micromolar affinities. This community is not edited and does not necessarily reflect the views of Nature Portfolio. Online ahead of print. The emergence of a common progenitor cell has been postulated for the association of CD30-positive lymphoproliferative disease (LPD) and mycosis fungoides (MF) within the same patient. 50-75% of myeloma patients exhibit translocations at the immunoglobulin heavy chain (IgH) locus juxtaposing oncogenes from partner chromosome. Replacement to Abcam, Santa Cruz, Sigma and CST antibody. It is reactive with human, mouse and rat. The investigators examined the records of 3 024 340 Swedish was IRF4 rs12203592 (p=0·002). EGFR is a protein that is found on the surface of some cells that causes cells to divide when epidermal growth factor binds to it. This aberrant growth depends on a regulatory protein called IRF4. Mechanistically, IRF4 overexpression expands a myeloma progenitor population, while IRF4 inhibition impairs cell survival via cell cycle arrest and sensitization to clinical myeloma. Romesser,1,2 andLouisM. For example, in breast cancer, prostate cancer and melanoma, the CAFs-mediated reverse Warburg effect, where CAFs undergo anaerobic glycolytic activity to release lactate to nearby tumor cells, has been reported -13]. A, Microarray analysis demonstrating the genes that were upregulated and downregulated after IRF4 ablation. 2014;21:888-903 pubmed publisher Vatolin S, Khan S, Reu F. IRF4 allows myeloma stem cells to proliferate and survive and higher levels of IRF4 are associated with a lower overall survival prognosis. Western blot analysis was performed using IRF4 / MUM1 antibody (GTX129135) diluted at 1:500. Background: Multiple myeloma (MM) is the second most common hematological malignancy and an incurable bone marrow cancer so far. In addition, the activity of these proteins can regulate the expression of osteoclastogenic cytokines during cancer progression. Adelson Medical Research Foundation, the Riney Family Myeloma Initiative, and the National Natural Science Foundation of China (NSFC grant no. Now, let’s see, the full “Nature” study starts with a discussion of a genetic method to identify therapeutic targets in cancer in which small hairpin RNAs (shRNAs) that mediate RNA interference are screened for their ability to block cancer cell proliferation and/or survival. David Baltimore's lab contains the insert Mouse IRF4 and is published in Blood. 0001), and MSC (p < 0. rs872071 is a SNP associated with the interferon regulatory factor 4 IRF4 gene. Ion AmpliSeq Comprehensive Cancer Panel target gene list ABL1 ABL2 ACVR2A ADAMTS20 AFF1 AFF3 AKAP9 AKT1 AKT2 AKT3 ALK APC AR IRF4 IRS2 ITGA10. 49 An essential caveat of these analyses was the use of germline. IRF4 ELISA Kits. The expression of IRF4 in human malignancies mirrors its expression in lymphoid activation and differentiation. It has been found that transcription factors (TF) dysregulation, leading to the significant expression modifications of genes, is a widely distributed phenomenon regarding human malignant neoplasias. Mouse insertional mutagenesis experiments support the designation of IRF4 as a cancer causing gene. Cancer Res 76, 513-516. This is how we discovered that the promoter of IRF4, a transcription factor involved in hematological cancers, is heavily methylated in many types of cancer. If treatment doesn't destroy all of the abnormal cells, then there is a good chance the cancer will come back stronger. First, a pool of gene expression profile datasets obtained from different types of hematological malignancies were analyzed for genes whose expression is correlated with IRF4 using the. IRF4-Targeted Therapies for Cancer, Transplant Rejection, and Autoimmune Disorders This invention is a method of depleting or over-expressing the transcription factor, interferon regulatory factor 4 (IRF4), in T cells as therapeutic strategy for conditions which are highly regulated by the immune system. Studies have shown a connection between the synthesis of proteins, known as IRF4, and low patient survival rates. Here, we have investigated the mechanism that activates these cells and the contribution of the intestinal microbiota for POI induction. b Resazurin proliferation assay at 7 days post-treatment. Inhibitors of transcriptional coactivators that regulate AR activity, including the paralog histone acetyltransferase proteins p300 and CBP, are attractive therapeutic targets for lethal prostate cancer. 1 We, thus, performed a detailed fluorescence in situ hybridisation study using three-colour probes of mixed 6p25. Tonsillar follicular large B-cell lymphoma with IRF4 rearrangement causing sleep apnea Yu -Ting Yu,1 Seiji Sakata,2 Kengo Takeuchi,2,3 L. Lymphocyte-specific interferon regulatory factor (LSIRF) (now called IRF4) is a transcription factor expressed only in lymphocytes. IRF4 was critical in all 8 PEL cell lines tested, and surprisingly, IMiDs triggered downregulation of IRF4 expression independently of both IKZF1 and IKZF3. Cancer immunotherapy relies on getting T cells —the immune system's primary killers of infected and diseased cells—to attack and kill tumor cells. 1 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. MUM1) genes by Fluorescence in situ Hybridization (FISH). Mosser DM and Edwards JP (2008). differentiation, relies on IRF4 [27, 28]. Cancer Immunology, Immunotherapy (2020) 69:2101-2112 2105 1 3 IRF4 (MFI x 10 2) 10 8 6 4 2 0-+ -+ + Tumor status Isotyp e Blood Splee n Tu mo r PMN-MDSC a b Coun t Blood Spleen Tu mor. In T cells, IRF4 is required for the. The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ Tregs in tumors are not well known. Professor Stephen Nutt, Walter & Eliza Hall Institute of Medical Research. Microglial IRF5 and IRF4 Expression Corresponded to Different Profiles of Cytokine Production in an Oxygen-Glucose Deprivation Model. The Q9-343 monoclonal antibody specifically recognizes human and mouse Interferon Regulatory Factor 4 (IRF4 or IRF-4) which is also known as Lymphocyte specific interferon regulatory factor (LSIRF), Multiple myeloma oncogene 1 (MUM1), or PU. SNP is predictive of melanoma subtypes. 1-3 Current challenges in the clinical success of cancer therapy result from limitations in the interventional mechanisms themselves. IRF4: Immunity. Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data. A new, targeted approach to the treatment of myeloma silences IRF4, a gene that allows myeloma stem cells and tumor cells to proliferate and survive. Cancer immunotherapy relies on getting T cells —the immune system's primary killers of infected and diseased cells—to attack and kill tumor cells. BMC Cancer, 7:226. For prostate cancer, this includes abiraterone and enzalutamide. Up to now no comprehensive analysis has yet addressed the genetic profiles of such concurrent lymphoma subtypes. The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival. This FISH test identifies rearrangements involving the locus. then supplemented the multiple myeloma cells with extra IRF4 or Myc while treating with the inhibitors and found that this caused the inhibitors to lose most of their effect. Plus, IRF4 is involved in various inflammatory responses to microbial pathogens such as muramyl dipeptide (MDP) or lipopolysaccharide (LPS). According to the study, the transcription factor IRF4 drives T cell differentiation and immunosuppression in multiple human cancers. Validated for ELISA, ICC, IF, IHC and WB. Designed to kill cancer. In colon cancer cells and fibroblasts,. The expression of IRF4 in human malignancies mirrors its expression in lymphoid activation and differentiation. This M00401-1 anti-MUM1/IRF4 Rabbit Monoclonal antibody, Clone#RM352 is validated on raji cell lysate, human melanoma tissue, thyroid cancer tissue. Patients that are alive at last time for. Large B-cell lymphoma with IRF4 rearrangement is a provisional entity in the 2017 World Health Organization classification. Please note the number of articles fluctuates since newly identified citations are added and citations for discontinued catalog numbers are removed. Immunohistochemistry-Paraffin: IRF4 Antibody [NBP1-82814] - Staining of human kidney shows no postivity in cells in tubules as expected. The aim of this study is to investigate whether IRF4 participates in the immune response in colon cancer. In addition, the activity of these proteins can regulate the expression of osteoclastogenic cytokines during cancer progression. Epub 2016 May 4. Borbet, Timothy C; Zhang, Xiaozhou; Müller, Anne; Blaser, Martin J (2019). 0001), ELMO1 (p < 0. MUM1 (multiple myeloma oncogene-1)/IRF4 (interferon regulatory factor 4) is a 50 kDa protein encoded by MUM1 gene, and a member of the interferon regulatory factor family of transcription factors. DF6198 at 1/100. TolgaEmre, 1PaulB. Although timely treatments such as surgery, chemotherapy and radiotherapy can prolong the overall survival of. There are several variants of Mantle cell lymphoma. Description. It is guaranteed to work for IHC, WB in human. 1-3 Current challenges in the clinical success of cancer therapy result from limitations in the interventional mechanisms themselves. Finally, miR-99b expression was lower in TAMs of patients with liver cancer than that in adjacent tissues, while the expression of κB-Ras2 and mTOR was reversed. 2016 Jul;6(7):714-26. The vast majority of breast cancers are carcinomas that originate from cells lining the milk-forming ducts of the mammary gland. The role of the changing human microbiome in the asthma pandemic. , IRF4 and Myc. First, a pool of gene expression profile datasets obtained from different types of hematological malignancies were analyzed for genes whose expression is correlated with IRF4 using the. 01% of AACR GENIE cases, with cancer of unknown primary, dedifferentiated liposarcoma, and pancreatic adenocarcinoma having the greatest prevalence []. Although IRF4 translocations establish its oncogenic potential, cancer cells can be dependent upon IRF4 even if the IRF4 locus is not genetically altered (see below). 1 interaction partner (PIP). lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. IRF4 is a transcription factor, a protein that helps to activate other genes. BMC cancer 12, 306-314. X-axis shows time for survival (years) and y-axis shows the probability of survival, where 1. Cancer types: Multiple myeloma and Waldenström macroglobulinemia What's analyzed: Blood and urine How used: To help diagnose disease, assess response to treatment, and look for recurrence. DF6198 at 1/100. The roles of IRF4 in regulating the CD8+ T cell response to cytokines have not been explored. Expression of IRF4 (LSIRF, MUM1) in cancer tissue. If nothing else, IRF4 is linked with cancer and it's unlikely anyone would want to swap youthful locks for a higher cancer risk. Multiple myeloma is a plasma cell neoplasm and the second most common hematologic cancer, with over 30,000 Americans diagnosed each year. IRF4 Antibody detects endogenous levels of total IRF4. 2021: IRF4-dependent upregulation of interleukin 9 protein is associated with ulcerative colitis pathogenesis. Photo credit: NIAID/NIH A new study, published August 13, 2018, in Cancer Cell, has uncovered the critical importance of a complex of proteins, called BATF3 and IRF4, in regulating a pro-growth and survival network in adult T-cell leukemia/lymphoma (ATLL). Expression of IRF4 in liver cancer - The Human Protein Atlas. B cell lymphoma is not one disease but a few dozen heterogeneous diseases, or individual cancers, that affect the b-cells in the lymphatic system. IRF4/DUSP22 Gene Rearrangement. Journal of Allergy and Clinical Immunology, 144 (6):1457-1466. It binds to and activates the ISRE of the MHC class I. EGFR is found at abnormally high levels in cancer cells, and EGFR activation appears to be important in tumor growth and progression. Plus, IRF4 is involved in various inflammatory responses to microbial pathogens such as muramyl dipeptide (MDP) or lipopolysaccharide (LPS). Strong IRF4/DUSP22 expression is usually seen with BCL6 and a high proliferation index. The hallmark of myeloma is chromosomal translocations that transform plasma cells into malignant myeloma cells. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non-small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. So, what we saw is that the drug was working—but that, in high density settings, there still remained enough IRF4 for the MYC to be produced and the cancer to continue its proliferation. The primer mix has been tested to generate satisfactory qPCR data on ABI 7900HT. CPEB4 and IRF4 expression in peripheral mononuclear cells are. The molecular determinants of the resistance have been extensively studied, but these discoveries have not yet been translated into therapeutic benefits. 34% of all cancers with colon adenocarcinoma, lung adenocarcinoma, breast invasive ductal carcinoma, diffuse large B-cell lymphoma, not otherwise specified, and cutaneous melanoma having the greatest prevalence of alterations. IRF4 is induced by cold and cAMP in adipocytes and is sufficient to promote increased thermogenic gene expression, energy expenditure, and cold tolerance. rs12203592 Disrupts a Conserved Melanocyte Enhancer at IRF4 (A) UCSC genome browser view shows 25 kb region around IRF4 (hg19 coordinates chr6:388,750–413,750). There are several variants of Mantle cell lymphoma. 8 NF-κB has been identified as a. 19 In T cells, IRF4 is crucial for T-cell differentiation and expansion, 20-24 in dendritic cells IRF4 contributes to the regulation. IRF4 antibody can be used for detection of IRF4 by western blot at 0. However, the biological role of IRF4 in colon cancer is still unclear. The molecular subtypes of breast cancer, which are based on the presence or absence of hormone receptors (estrogen and progesterone subtypes. 1,2 It is composed of an N-terminal DNA binding domain, a linker domain, an interferon activation domain, and a C-terminal autoinhibitory. In contrast to the IRF4- counterparts, IRF4+ Tregs expressed a vast array of suppressive molecules, and their presence correlated with multiple exhausted subpopulations of T cells. tumor cell line T110299, which originate from a genetically. Funding period: 2019 - 2022. Ionis teamed up with researchers at the University of California, San Diego to inhibit the gene IRF4 in multiple myeloma using an antisense oligonucleotide. Keywords:Liver cancer, AuNPs, TiO 2 NPs, nanocarrier, ERL, erlotinib, IRF4, nanoparticles. We aimed to delineate the molecular alterations of clonally related CD30-positive LPD and MF. Western blot analysis was performed using IRF4 / MUM1 antibody (GTX129135) diluted at 1:500. 0001), CLIP4 (p < 0. Kyu HH, Bachman VF, Alexander LT, et al. Combined single nucleotide polymorphism-based genomic mapping and global gene expression profiling identifies novel chromosomal imbalances, mechanisms and candidate genes important in the. IRF4 dependency in myeloma is an example of 'non-oncogene addiction', where cancer cells depend on a normal cellular protein for proliferation and/or survival. IRF4 IRS2 ITGA10 ITGA9 ITGB2 ITGB3 JAK1 JAK2 JAK3 JUN KAT6A KAT6B KDM5C KDM6A KDR KEAP1 KIT KLF6 KRAS LAMP1 LCK LIFR LPHN3 POT1 LPP LRP1B LTF LTK MAF MAFB MAGEA1 MAGI1 MALT1 MAML2 MAP2K1 MAP2K2 MAP2K4 MAP3K7 MAPK1 MAPK8 MARK1 Ion AmpliSeq ™ Comprehensive Cancer Panel target gene list. IRF4 WT bound ISRE DNA with a binding affinity (K D) of 0. Whereas IRF4 has been extensively studied in B cells, comparatively little is known about the function of IRF4 in T cells. Improving Cancer Immunotherapy: Overcoming the Problem of 'Exhausted' T Cells. IRF4, interferon regulatory factor 4, belongs to the IRF family of transcription factors and is a critical transcriptional regulator of immune system development and function [ 24 ]. The aim of this study is to investigate whether IRF4 participates in the immune response in colon cancer. Cre-mediated GFP expression was used to trace Irf4 ablation with other markers (CD11c, CD11b and CD8α) in splenocytes (Klein et al. sis revealed that combination treatment depleted IRF4 and c-MYC to the greatest extent in comparison to either single agent treatment. Gene of 19,4 kb with 9 exons and 8 introns. IRF4 plays essential roles in the regulation of innate and adaptive immune responses. IRF4 belongs to the IRF (interferon regulatory factors) family of transcription factors and is a critical transcriptional regulator of immune system development and function. Immunohistochemistry-Paraffin: IRF4 Antibody [NBP1-82814] - Staining of human tonsil shows strong nuclear positivity in non-germinal center. Rabbit IRF4 Rabbit pAb (A0524), validaed in WB and tested in Human,, Mouse,, Rat. Cancer Res 76, 513-516. Epub 2016 May 4. Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels, coordinating both immunogenic and tolerogenic immune responses. Associated Content An unexpected. Clinical Significance Gene rearrangements involving the DUSP22-IRF4 gene region have been reported in CD30-positive, ALK-negative anaplastic large cell lymphoma and are associated with a favorable clinical outcome. 0 corresponds to 100 percent. Researchers at University of California San Diego School of Medicine and Ionis Pharmaceuticals are taking a new, targeted approach to myeloma treatment — silencing IRF4, a gene that allows myeloma stem cells and tumor cells to proliferate and survive. 52,53 KLF4-induced P21. ABclonal provides trial size antibody samples for target detection. IRF4 antibody LS-B7104 is an unconjugated rabbit polyclonal antibody to IRF4 from human. Among them, low expression of IRF4 is associated with poor prognosis of cervical cancer. 91 x 10e-20) of all SNPs studied. Adaptive immune resistance is a process in which the cancer changes its phenotype in response to a cytotoxic or proinflammatory immune response, thereby evading it. This article was originally published here FEBS J. IRF4 instructs effector Treg differentiation and immune suppression in human cancer. 1 and BATF3, respectively, also expressed in these cells. NeoGenomics is a premier cancer diagnostics and pharma services company offering innovative diagnostic, prognostic and predictive testing. Past studies have shown that high IRF4 levels are associated with lower overall survival. Interferon regulatory factor 4 (IRF4), also known as MUM1 and LSIRF, is a 51 kDa lymphocyte-restricted transcription factor. Association of IRF4 SNP rs12203592 with melanoma-specific survival. Corresponding IRF4 RNA-seq data are presented for the same tissues. 100% Guaranteed. Large B-cell lymphoma with IRF4 rearrangement is a recently described, low-grade entity that occurs most commonly in children and young adults. Outside the B-. (Blood, Jan 2020) Wong R 1, Tan TK 2, Amanda S 3, Ngoc PCT 4, Leong WZ 5, Tan SH 6, Asamitsu K 7, Hibi Y 8, Ueda R 9, Okamoto T 8, Ishida T 10, Iida S 11, Sanda T 6. Romesser,1,2 andLouisM. IRF4, previously linked to effector Treg differentiation in murine tissues in physiology , is now shown to control the formation of ICOS + effector Tregs in the TME that, in turn, favor tumor growth in a mouse model of cancer. Blocking the production of this protein can be strikingly effective in eliminating cancer cells in laboratory. leading to IRF4 activation in each cancer context (Figure 1). 4 MM cell survival is strongly dependent on IRF4 and MYC, and MYC is a direct target gene of IRF4 transactivation, while IRF4 is a direct target of MYC. 7 year old Chinese boy with IRF4 / MUM1 positive lymphoma with strong and extensive CD5 and CD10 positivity (Pediatr Blood Cancer 2017;64:311) 12 year old boy with large B cell lymphoma with IRF4 rearrangement in the unusual location of inguinal region (Indian J Pathol Microbiol 2018;61:271). Conery et al. Ablation of FOXO1 was found to abolish binding of PR to the shared binding interval downstream of the IRF4 gene. So, what we saw is that the drug was working—but that, in high density settings, there still remained enough IRF4 for the MYC to be produced and the cancer to continue its proliferation. Cytoplasmic 5 weeks 12 weeks extracts were negative for IRF4 and are not shown. Naive WT and IRF4-KO CD4 + T cells were activated in Th1-inducing conditions in vitro for 4 d prior to flow cytometry. then supplemented the multiple myeloma cells with extra IRF4 or Myc while treating with the inhibitors and found that this caused the inhibitors to lose most of their effect. Nature Portfolio makes no representations, warranties or guarantees. IRF4 is a member of the interferon regulatory factor (IRF) family of transcription factors and exerts critical functions in various cell types of the immune system (De Silva et al. BIRF4 (Blood Sample): Fluorescence in Situ Hybridization (FISH) is performed uisng IRF4 break-apart FISH probe to detect IRF4 rearrangement from leukemic blood samples. exert effects on human non-small cell lung cancer (NSCLC) and to explore the underlying mechanism. Heightened expression and function of the transcription factor IFN regulatory factor 4 (IRF4) accompany enhanced anabolic induction and full commitment to functional differentiation in B cells and CD8+ T cells. IRF4: Immunity. Malignancy! Therapy? Clinical Cancer Research - United States doi 10. IRF4 also enhances DNA binding by the E2A-encoded gene product E47 and functions synergistically to activate transcription from the Igκ 3′ enhancer. Tested on 20 paraffin-embedded human tissues. According to global cancer statistics in 2018, lung cancer accounts for ~12% of newly diagnosed cancer cases and ~18% of total cancer deaths (). Journal of Immunology, 205(7):1933-1943. Associated Content An unexpected. Validated for ELISA, ICC, IF, IHC and WB. In addition, the activity of these proteins can regulate the expression of osteoclastogenic cytokines during cancer progression. IRF4 expression defines intratumoral Treg heterogeneity. SNP is predictive of melanoma subtypes. Dysregulated Nucleotide Excision Repair (NER) Is a New Target in Multiple Myeloma. IRF4 gene rearrangement. Jesse Boehm's lab contains the insert IRF4 and is published in Cancer Discov. Ionis teamed up with researchers at the University of California, San Diego to inhibit the gene IRF4 in multiple myeloma using an antisense oligonucleotide. According to the National Cancer Institute, multiple myeloma is the second most common blood cancer in the US, with more than 32,000 new cases predicted in 2020 and a five-year survival of only 53. Center for Cancer Research National Cancer Institute Building 10, Room 5A02 Bethesda, MD 20892 Ph: 240-781-3394 [email protected] The ELISA (enzyme-linked immunosorbent assay) is a widely used application for detecting and quantifying proteins and antigens from various samples. (C) Cellularity of spleen and lymph nodes in IRF4-'- mice. Since IRF4 is a "context-dependent" factor, it is necessary to analyze the patterns of gene expression associated with IRF4 in individual cancer types. Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) represents approximately 5% of Hodgkin lymphoma and typically affects children and young adults. Prof Nutt will employ a novel approach to identify and test drugs that can inhibit IRF4 and block the growth of MM cells. 0001), ELMO1 (p < 0. Western blot analysis was performed using IRF4 / MUM1 antibody (GTX129135) diluted at 1:500. 2015 Jun 1; 24(11): 3296-303. The investigators examined the records of 3 024 340 Swedish was IRF4 rs12203592 (p=0·002). LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B, and MYD88), losses of 17p13 and gains of chromosome 7, 11q12. RT-qPCR analysis of IRF4 transcripts (A) in all epidermal skin samples and (B) in only light epidermal skin samples with either the rs12203592 CC-genotype (all: n = 25; lights: n = 13) or with the combinational rs12203592 CT- and TT-genotypes (n = 4) demonstrates reduced IRF4 expression when the T-allele is present. IRF4 and IRF8 are immune-system specific members of the IRF family of transcriptions factors that have crucial and diverse functions in regulating B and T lymphocytes as well as macrophages and dendritic cells. Interleukin-22: A Regulator of Intestinal Immune Responses in Cancer and Autoimmunity. d 2 days post-treatment with 10 μM ASOs. 2012 Oct 1;189(7):3368-77. 26 revealed lowered. Blocking the production of this protein can be strikingly effective in eliminating cancer cells in laboratory. Genetic deletion of IRF4 was found in miR-125b-induced B-cell cancer, but its role in oncogenic miR-125b-induced B-cell transformation is still unknown. Gene of 19,4 kb with 9 exons and 8 introns. 1 We, thus, performed a detailed fluorescence in situ hybridisation study using three-colour probes of mixed 6p25. The information in the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer relates cytogenetic changes and their genomic consequences, in particular gene fusions, to tumor characteristics, based either on individual cases or associations. Langerhans cells (LC) can prime tolerogenic as well as immunogenic responses in skin, but the genomic states and transcription factors (TFs) regulating these context-specific responses are unclear. IRF4 is a gene located on chromosome 6 that encodes for the IRF4 protein belonging to the IRF family of transcription factors. Nature Portfolio makes no representations, warranties or guarantees. However, the biological role of IRF4 in colon cancer is still unclear. Large B-cell lymphoma with IRF4 rearrangement constitutes a novel provisional entity included in the classification of lymphoid tissue recently proposed by the World Health Organization in its fourth revised edition. IRF4 is known as a regulator of T-cell differentiation which is activated by NFkB, NFAT and TLR4 signaling [46,47,48,49,50,51]. Among its related pathways are Preimplantation Embryo and IL4-mediated signaling events. Cre-mediated GFP expression was used to trace Irf4 ablation with other markers (CD11c, CD11b and CD8α) in splenocytes (Klein et al. IRF4 is widely expressed in leucocytes and is essential for the development, activation, differentiation, and/or apoptosis of T helper (Th) cell subsets including Th2, Th9, Th17, T follicular helper (Tfh) cells, or T (Treg) cells. It is guaranteed to work for IHC, WB in human. IRF4 directly represses IRF8 and upregulates SHIP gene expression that results in stronger BCR-induced calcium. Cancer Panel v2; these genes are indicated in dark grey cells. 1093/hmg/ddt142: Do T N. 1158/2159-8290. a Resazurin proliferation assay of cells treated for 7 days with 20 μM IRF4#1 normalized to cells treated with Control ASO. Early CRC detection is key and is associated with improved survival outcomes. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013. Indeed, our in vitro studies confirm a role for IL-21 in reducing IRF4 and. However, the most common type of b cell lymphoma is diffuse large b-cell lymphoma (DLBCL), and researchers have come up with a rather handy method of determining prognosis for people with DLBCL ( Diffuse Large B Cell Lymphoma life expectancy). In addition, IRF4 has an essential role in the differentiation of macrophages [29]. Interferon regulatory factor 4 (IRF4) is a transcription factor from the IRF factor family that exerts regulatory functions in the immune system and oncogenesis. "These proof-of-principle studies will enable rapid clinical development of anti-sense oligonucleotide-mediated IRF4 inhibition to prevent myeloma relapse driven by drug-resistant cancer stem cells," said co-senior author Catriona Jamieson, MD, PhD, Koman Family Presidential Endowed Chair in Cancer Research, deputy director of Moores Cancer. Replacement to Abcam, Santa Cruz, Sigma and CST antibody. The TF IRF4 is involved in regulating the number and function of CD8+ T cells,29-32 influencing their differentiation, expansion30, 33 and metabolism. 10 IRF4 binds only weakly to DNA and thus interacts in T-cells with other transcription factors such as JUN. Objective Postoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. High-dimensional single-cell profiling of T cells from chemotherapy-naive individuals with non-small-cell lung cancer identified the transcription factor IRF4 as specifically expressed by a subset of intratumoral CD4+ effector Tregs with superior suppressive activity. There are several variants of Mantle cell lymphoma. Nature Portfolio makes no representations, warranties or guarantees. It is aimed to help Labome visitors find the most suited IRF4 antibody. IRF4 is induced by Toll-like receptor (TLR) activation and acts as a negative regulator of TLR signaling. MYC Comparison of survival outcomes revealed that the IRF4/MUM1-positive group exhibited worse survival than the IRF4/MUM1- negative group; moreover, I RF4/MUM1-positive patients with a high. Borbet, Timothy C; Zhang, Xiaozhou; Müller, Anne; Blaser, Martin J (2019). Corresponding IRF4 RNA-seq data are presented for the same tissues. Reprogramming. The mRNA and protein expression of IRF4 was detected in NSCLC tissues using reverse-transcription quantitative polymerase chain reaction and western blotting, respectively. More research is needed to determine the mechanism by which IRF4 is involved in how melanocytes respond to UV damage, which can induce freckling and is linked to melanoma, the type of skin cancer associated with the highest mortality. B cell lymphoma is not one disease but a few dozen heterogeneous diseases, or individual cancers, that affect the b-cells in the lymphatic system. Ionis teamed up with researchers at the University of California, San Diego to inhibit the gene IRF4 in multiple myeloma using an antisense oligonucleotide. Therefore, it is important to develop means for targeting the multiple myeloma bone marrow microenvironment. The 'lollipop plot' above illustrates recurrent (observed in 3 or more out of 4440 TCGA tumor samples from 15 cancer types) and therefore potentially oncogenic missense mutations (click on 'Show Cancer Mutations'). IRF4 Antibody detects endogenous levels of total IRF4. Gene of 19,4 kb with 9 exons and 8 introns. d 2 days post-treatment with 10 μM ASOs. An initial impression of paediatric-type follicular lymphoma was considered but the strong expression of MUM1/IRF4 suggests the alternative entity ─ follicular form of large B-cell lymphoma with IRF4 rearrangement. 1Rdf (conditional) Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO). IRF4: Immunity. Designer DNA Therapeutic Wipes Out Cancer Stem Cells, Treats Multiple Myeloma in Mice Study supports launch of Phase I clinical trial to test a designer DNA agent — an antisense oligonucleotide that targets a gene called IRF4 — in patients with multiple myeloma. A new, targeted approach to the treatment of myeloma silences IRF4, a gene that allows myeloma stem cells and tumor cells to proliferate and survive. IRF4 directly represses IRF8 and upregulates SHIP gene expression that results in stronger BCR-induced calcium. Irf4 is a critical regulator of many aspects of B- and T-cell differentiation and cell metabolism (Biswas et al. IRF4 / MUM1 antibody was raised against a 16 amino acid synthetic peptide near the carboxy terminus of human IRF4 / MUM1. Impaired Th1 differentiation in IRF4-KO CD4 + T cells. 1,2 It is composed of an N-terminal DNA binding domain, a linker domain, an interferon activation domain, and a C-terminal autoinhibitory. IRF4, previously linked to effector Treg differentiation in murine tissues in physiology , is now shown to control the formation of ICOS + effector Tregs in the TME that, in turn, favor tumor growth in a mouse model of cancer. , SFRP2 and IRF4) that confirms the reliability of our screening method (13, 30). Past studies have shown that high IRF4 levels are associated with lower overall survival rates for patients with the disease. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. Ning's Lab has two well-equipped lab rooms with a total of approximate 1,000 sq, ft, and also has a separate cell culture room. BMC Cancer, 7:226. Conversely, knockout of IRF4 in UCP1(+) cells causes reduced thermogenic gene expression and energy expenditure, obesity, and cold intolerance. Journal of Immunology, 205(7):1933-1943. Miriam and Sheldon G. The strategy provides an earlier opportunity to target cancer cells that may have spread throughout the body without detection, BMS said. It is reactive with human, mouse and rat. In line with this expression pattern, tissue-resident CD4. Ablation of FOXO1 was found to abolish binding of PR to the shared binding interval downstream of the IRF4 gene. In MM, the secondary copy number changes of the positive cases are unknown. IRF4 is a gene located on chromosome 6 that encodes for the IRF4 protein belonging to the IRF family of transcription factors. Therefore, it is important to develop means for targeting the multiple myeloma bone marrow microenvironment. Denny JC, Bastarache L, Ritchie MD et al. Large B-cell lymphoma with IRF4 rearrangement is a provisional entity in the 2017 World Health Organization classification. ITGA9 ITGB2 ITGB3 JAK1 JAK2 JAK3 JUN KAT6A KAT6B KDM5C KDM6A KDR KEAP1 KIT KLF6 KRAS LAMP1 LCK LIFR LPHN3 POT1 LPP LRP1B LTF LTK MAF. Giorgia Alvisi, Jolanda Brummelman, Simone Puccio, Emilia MC Mazza, Elisa Paoluzzi Tomada, Agnese Losurdo, Veronica Zanon, Clelia Peano, Federico S Colombo, Alice Scarpa, Marco Alloisio, Ajithkumar Vasanthakumar, Rahul Roychoudhuri, Marinos Kallikourdis. BMS is exploring the use of its immunotherapy treatments at earlier stages of cancer in the neoadjuvant, adjuvant and peri-operative settings, as well as with chemoradiation. The aim of this study is to investigate whether IRF4 participates in the immune response in colon cancer. Dürig, J; Bug, S; Klein-Hitpass, L; Boes, T; Jöns, T; Martin-Subero, J I; Harder, L; Baudis, Michael; Dührsen, U; Siebert, R (2007). Irf4 is a critical regulator of many aspects of B- and T-cell differentiation and cell metabolism (Biswas et al. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013. IRF4 interferon regulatory factor 4. 1 interaction partner (PIP). The cancer tissue page shows antibody staining of the protein in 20 different cancers. Robust cytotoxic CD8+ T-cell response is important for immunity to intracellular pathogens. Figure 7 a-b display the immunohistochemical images of IRF4 in normal tissues and cervical cancer tissues based on the HPA database. Probably plays a role in ISRE-targeted signal transduction mechanisms specific to lymphoid cells. Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma: Iida S, Rao PH, Butler M, Corradini P, Boccadoro M, Klein B, Chaganti RS, Dalla-Favera R: Nat Genet 1997 Oct;17(2):226-30: PMID 9326949 : Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and. Ning's Lab has two well-equipped lab rooms with a total of approximate 1,000 sq, ft, and also has a separate cell culture room. Reprogramming. Cancer types: Lymphoma What's analyzed: Tumor How used: To help in diagnosis. Gene-expression profile analysis has also revealed that. This section gives an overview of IRF4, along with links to any related data and resources. Since the early 2000s, outcomes for patients have improved with the devel-. Interferon Regulatory Factor 4 (IRF4) is a transcription factor which plays a critical role in the differentiation of normal B and. IRF4 Antibody detects endogenous levels of total IRF4. Microglial IRF5 and IRF4 Expression Corresponded to Different Profiles of Cytokine Production in an Oxygen-Glucose Deprivation Model. Transcriptional activator. Multiple myeloma is a plasma cell neoplasm and the second most common hematologic cancer, with over 30,000 Americans diagnosed each year. The differences between WT IRF4 and empty vector, between K59R IRF4 and empty vector, and between WT IRF4 and K59R IRF4 were statistically significant. P300/CBP inhibition also impacts IRF4, which is important in certain haematological malignancies. According to the National Cancer Institute, multiple myeloma is the second most common blood cancer in the United States, with more than 32,000 new cases predicted in 2020 and a five-year survival. These antibodies target IRF4 in Human, Mouse, Rat, Porcine and Non-human primate samples. (C) Cellularity of spleen and lymph nodes in IRF4-'- mice. The new treatment uses an engineered piece of DNA (an antisense oligonucleotide) specifically designed to bind the genetic material coding of IRF4. But there's an important stumbling block for. Ighg1 tm1(cre)Cgn /Ighg1 + Irf4 tm1Rdf /Irf4 tm1. Therefore, the disease still remains incurable and new more efficacious therapies are needed. Designer DNA Therapeutic Wipes Out Cancer Stem Cells, Treats Multiple Myeloma in Mice Study supports launch of Phase I clinical trial to test a designer DNA agent — an antisense oligonucleotide that targets a gene called IRF4 — in patients with multiple myeloma. Interferon regulatory factor 4 also known as MUM1 is a protein that in humans is encoded by the IRF4 gene, located at 6p25-p23. It is required for immunoglobulin class switching and terminal differentiation of B cells. IRF4 was critical in all 8 PEL cell lines tested, and surprisingly, IMiDs triggered downregulation of IRF4 expression independently of both IKZF1 and IKZF3. 19 In T cells, IRF4 is crucial for T-cell differentiation and expansion, 20-24 in dendritic cells IRF4 contributes to the regulation. PMID 28251349. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The cancer tissue page shows antibody staining of the protein in 20 different cancers. However, the biological role of IRF4 in colon cancer is still unclear. ABSTRACT Multiple myeloma is a malignancy of plasma cells that grow within the bone ma. IRF4 Expression Is Required for the Immunoregulatory Activity of Conventional Type 2 Dendritic Cells in Settings of Chronic Bacterial Infection and Cancer. This is a Validated Antibody Database (VAD) review about human IRF4, based on 42 published articles (read how Labome selects the articles), using IRF4 antibody in all methods. IRF4 instructs effector Treg differentiation and immune suppression in human cancer. Mechanistically, IRF4 overexpression expands a myeloma progenitor population, while IRF4 inhibition impairs cell survival via cell cycle arrest and sensitization to clinical myeloma. BIRF4 (Blood Sample): Fluorescence in Situ Hybridization (FISH) is performed uisng IRF4 break-apart FISH probe to detect IRF4 rearrangement from leukemic blood samples. The RCSB PDB also provides a variety of tools and resources. The immunogen is located within the last 50 amino acids of IRF4. IRF4 expression defines intratumoral Treg heterogeneity. a Resazurin proliferation assay of cells treated for 7 days with 20 μM IRF4#1 normalized to cells treated with Control ASO. The replication set 1 consisted of 190 melanoma cases, 252 SCC cases, and 634 common controls. We found large induction of IRF4 and its targets also in HFD IL-21 KO adipose tissue both in the fasting and in the refeeding state. Description. The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ Tregs in tumors are not well known. Conjugation. IRF4 IRS2 ITGA10 ITGA9 ITGB2 ITGB3 JAK1 JAK2 JAK3 JUN KAT6A KAT6B KDM5C KDM6A KDR KEAP1 KIT KLF6 KRAS LAMP1 LCK LIFR Ion AmpliSeq ™ Comprehensive Cancer Panel. Online ahead of print. Interferon regulatory factor 4 (IRF4), also known as MUM1 and LSIRF, is a 51 kDa lymphocyte-restricted transcription factor. IRF4 expression is tightly regulated in resting primary T cells and plays an essential role in the homeostasis and function of mature lymphocytes. IRF4 is normally expressed in plasma cells, melanocytes, some B-cells. Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages; miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth. About 85% of diagnosed lung cancer is non-small cell lung cancer (NSCLC), which have a low 5-year survival rate (<15%) (2,3). Large B-cell lymphoma with IRF4 rearrangement constitutes a novel provisional entity included in the classification of. LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B, and MYD88), losses of 17p13 and gains of chromosome 7, 11q12. Borbet, Timothy C; Zhang, Xiaozhou; Müller, Anne; Blaser, Martin J (2019). Ighg1 tm1(cre)Cgn /Ighg1 + Irf4 tm1Rdf /Irf4 tm1. Among individuals with melanoma, there was a positive correlation (odds. In the model, MBD2 and IRF4 protein expression increased in the lung and spleen cells. In addition, the activity of these proteins can regulate the expression of osteoclastogenic cytokines during cancer progression. BMC Cancer, 7:226. Light chain variants t (2;6) (p12;p25), t (6;22) (p25;q11). , IRF4 and Myc. As such, a paradigm shift in melanoma treatment, to surmount the therapeutic impasses linked to the. Vincent Giguère and 1 other. IRF4 was significantly downregulated both at mRNA and protein levels by the phenpropyl ester analog that demonstrated a remarkable increase in cleaved caspase-3 levels and apoptotic cell number. Expression of IRF4 (LSIRF, MUM1) in cancer tissue. Systemic IRF4 deficiency accelerates PDAC tumor growth and expands MDSC in vivo. Cancer type: Certain types of. Furthermore, Th2-preferential in vivo binding of NFAT1 and IRF4 to the CNS-9 region was observed by ChIP. IRF4, previously linked to effector Treg differentiation in murine tissues in physiology , is now shown to control the formation of ICOS + effector Tregs in the TME that, in turn, favor tumor growth in a mouse model of cancer. According to the National Cancer Institute, multiple myeloma is the second most common blood cancer in the United States, with more than 32,000 new cases predicted in 2020 and a five-year survival. IRF4 instructs effector Treg differentiation and immune suppression in human cancer. Positivity for the rearrangement is a positive prognostic sign. Early CRC detection is key and is associated with improved survival outcomes. We aimed to delineate the molecular alterations of clonally related CD30-positive LPD and MF. Tier 1 genes have documented evidence of their relevance to cancer. The molecular mechanisms responsible for the high immunosuppressive capacity of CD4+ Tregs in tumors are not well known. If treatment doesn't destroy all of the abnormal cells, then there is a good chance the cancer will come back stronger. Design POI was induced by manipulating the intestine of mice, which selectively lack DCs, monocytes or macrophages. Jesse Boehm's lab contains the insert IRF4 and is published in Cancer Discov. B cells are a lineage of lymphocytes originally discovered in the Bursa of Fabricus in birds (hence the B in B cells). Prof Nutt will employ a novel approach to identify and test drugs that can inhibit IRF4 and block the growth of MM cells. Past studies have shown that high IRF4 levels are associated with lower overall survival rates for patients with the disease. This is how we discovered that the promoter of IRF4, a transcription factor involved in hematological cancers, is heavily methylated in many types of cancer. Here, we further demonstrated an interaction of the effects of miR-125b and IRF4 in cancer induction by showing that miR125b-induced B-cell leukemia was greatly accelerated in IRF4 homozygous. (C) Cellularity of spleen and lymph nodes in IRF4-'- mice. Myeloma-associated macrophages (MAM) in the bone marrow niche are M2 like. 8 NF-κB has been identified as a. 0001), and MSC (p < 0. The role of the changing human microbiome in the asthma pandemic. monocytogenes infection and generated decreased numbers of L. The molecular determinants of the resistance have been extensively studied, but these discoveries have not yet been translated into therapeutic benefits. RT–qPCR analysis of IRF4 transcripts (A) in all epidermal skin samples and (B) in only light epidermal skin samples with either the rs12203592 CC-genotype (all: n = 25; lights: n = 13) or with the combinational rs12203592 CT- and TT-genotypes (n = 4) demonstrates reduced IRF4 expression when the T-allele is present. Inhibition of BRD4 shortcuts the communication between SEs and target promoters with a subsequent cell-specific repression of oncogenes to which cancer cells are addicted and cell death. FITC-conjugated goat-anti-rabbit secondary antibodies were used for the analysis. 100% Guaranteed. The primer mix has been tested to generate satisfactory qPCR data on ABI 7900HT. Interferon regulatory factor 4 (IRF4) is a transcription factor from the IRF factor family that exerts regulatory functions in the immune system and oncogenesis. In the in vitro experiment, IRF4 expression was knocked down or overex-. However, the biological role of IRF4 in colon cancer is still unclear. Thus, the genomic programming of LCs for cross-presentation is independent of IRF8 and instead appears to utilize IRF4 in combination with PU. The TF IRF4 is involved in regulating the number and function of CD8+ T cells,29–32 influencing their differentiation, expansion30, 33 and metabolism. Interferon regulatory factor 4 (IRF4) and IRF8 are evolutionarily diverged members of the IRF family of transcription factors (). At the time, the same team postulated that IRF4 could be a possible target for the development of myeloma immunotherapy. IRF4 belongs to the IRF (interferon regulatory factors) family of transcription factors and is a critical transcriptional regulator of immune system development and function. Cancer type: Certain types of. MUM1/IRF4 is also required for immunoglobulin class switch recombination (CSR). The replication set 1 consisted of 190 melanoma cases, 252 SCC cases, and 634 common controls. The molecular determinants of the resistance have been extensively studied, but these discoveries have not yet been translated into therapeutic benefits. The DUSP-IRF4 genetic rearrangement in ALCL confers a favourable prognosis in HIV-negative patients; it is unknown how this interacts clinically with HIV/AIDS. Plasmid pDONR223_IRF4_WT from Dr. IRF4 expression is tightly regulated in resting primary T cells and plays an essential role in the homeostasis and function of mature lymphocytes. They provide nurturing signals to multiple myeloma cells and promote immune escape. Objective Postoperative ileus (POI), the most frequent complication after intestinal surgery, depends on dendritic cells (DCs) and macrophages. EGFR inhibitors can be classified as either: tyrosine kinase inhibitors (TKI) (eg, erlotinib, gefitinib): these bind to the tyrosine kinase domain in the epidermal growth factor receptor and stop the activity of the EGFR. JAK2 gene mutation. expression of IRF4 has been linked to poor prognosis in myeloma involving the 14q32 translocation7 or those secreting immunoglobulin M. Using RNAseq and FACS, researchers analyzed tumor, adjacent normal tissue, and blood from lung cancer patients and found transcription factor IRF4 expression enhanced in a subset of Tregs, which correlated with poor prognosis and immunosuppressive phenotype in human and mice. IRF4 was determined to be a genomic target of both FOXO1 and PR and also to be differentially regulated in HESCs treated with small interfering RNA targeting FOXO1 or PR prior to decidualization stimulus. Therefore, it is important to develop means for targeting the multiple myeloma bone marrow microenvironment. ABSTRACT Multiple myeloma is a malignancy of plasma cells that grow within the bone ma. Conjugation. 1158/2159-8290. TESTED APPLICATIONS: ELISA, ICC, IF, WB: APPLICATIONS: IRF4 antibody can be used for detection of IRF4 by Western blot at 0. A, Microarray analysis demonstrating the genes that were upregulated and downregulated after IRF4 ablation. RT-qPCR analysis of IRF4 transcripts (A) in all epidermal skin samples and (B) in only light epidermal skin samples with either the rs12203592 CC-genotype (all: n = 25; lights: n = 13) or with the combinational rs12203592 CT- and TT-genotypes (n = 4) demonstrates reduced IRF4 expression when the T-allele is present. 2021: IRF4-dependent upregulation of interleukin 9 protein is associated with ulcerative colitis pathogenesis. IRF4 Reactivity: Human, Mouse, Rat, Cow, Dog, Guinea Pig, Horse, Rabbit, Zebrafish (Danio rerio) IHC, WB Host: Rabbit Polyclonal unconjugated anti-Interferon Regulatory Factor 4 (IRF4) (AA 342-451) antibody Primary Antibody. Up to now no comprehensive analysis has yet addressed the genetic profiles of such concurrent lymphoma subtypes. IRF4 is a gene located on chromosome 6 that encodes for the IRF4 protein belonging to the IRF family of transcription factors. The drug, called ION251, significantly. Past studies have shown that high IRF4 levels are associated with lower overall survival. It is guaranteed to work for IHC, WB in human. The strategy provides an earlier opportunity to target cancer cells that may have spread throughout the body without detection, BMS said. Ariela Noy 1, Lawrence Kaplan 2, Jeannette Lee 3, Ethel Cesarman 4 & Wayne Tam 4 Infectious Agents and Cancer volume 7, Article number: O14 (2012) Cite this article. To determine molecular switches directing induction of LC immune activation, we performed mathematical modelling of gene regulatory networks identified by single cell RNA sequencing of LCs exposed to TNF-alpha, a key pro-inflammatory. Whereas IRF4 has been extensively studied in B cells, comparatively little is known about the function of IRF4 in T cells. Outside the B-. Heo MH, Park HY, Ko YH, et al: IRF4/MUM1 expression is associated with poor survival outcomes in patients with peripheral T-cell lymphoma. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists. 6a and Supplementary. MUM1/IRF4 is expressed in the nuclei of plasma cells and a small percentage of germinal center (GC) B-cells located in the "light zone". Mouse (93%), Rat (92%). , 2012; De Silva, Simonetti, Heise, & Klein, 2012; Eguchi et al. BRD4, member of the Bromodomain and Extraterminal (BET) protein family, is largely acknowledged in cancer for its role in super-enhancers (SEs) organization and oncogenes expression regulation. POSITIVE CONTROL: 1) Cat. Plasmid pDONR223_IRF4_WT from Dr. 6% and 59% respectively. The mRNA and protein expression of IRF4 was detected in NSCLC tissues using reverse-transcription quantitative polymerase chain reaction and western blotting, respectively. In addition, our preliminary studies implicate IRF4 as a critical factor in melanoma cell proliferation and survival. It can be seen from the legend that in normal squamous epithelial cells, the staining level of IRF4 is low, the intensity is moderate, and the quantity < 25%. In addition, simvastatin, which suppresses IRF4 expression in MDSCs, could enhance the. Conventionally, cancer therapy has relied on various pharmacological and radiation-based interventions, often through means of chemotherapy and radiotherapy. 100% Guaranteed. 1 interaction partner (PIP). In vitro binding of NFAT1 and IRF4 to the CNS-9 region was observed by EMSA. 6a and Supplementary. In the in vitro experiment, IRF4 expression was knocked down or overex-. IRF4 has been shown to have a crucial role in lymphoid malignancy and is a well-known biomarker of activated B-cell like diffuse large B-cell lymphoma. The bone marrow niche has a pivotal role in progression, survival, and drug resistance of multiple myeloma cells. We aimed to delineate the molecular alterations of clonally related CD30-positive LPD and MF. A breakthrough: macrophage-directed cancer immunotherapy. IRF4 WT bound ISRE DNA with a binding affinity (K D) of 0.