{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:51:55Z","timestamp":1790218315470,"version":"4.1.0"},"reference-count":141,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016727","name":"Kishimoto Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004206","name":"Osaka University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004206","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    AT-rich interactive domain 5a (Arid5a) is a nucleic acid binding protein. In this review, we highlight recent advances in the association of Arid5a with inflammation and human diseases. Arid5a is known as a protein that performs dual functions. In\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies, it was found that an inflammation-dependent increase in Arid5a expression mediates both transcriptional and post-transcriptional regulatory effects that are implicated in immune regulation and cellular homeostasis. A series of publications demonstrated that inhibiting Arid5a augmented several processes, such as preventing septic shock, experimental autoimmune encephalomyelitis, acute lung injury, invasion and metastasis, immune evasion, epithelial-to-mesenchymal transition, and the M1-like tumor-associated macrophage (TAM) to M2-like TAM transition. In addition, Arid5a controls adipogenesis and obesity in mice to maintain metabolic homeostasis. Taken together, recent progress indicates that Arid5a exhibits multifaceted, both beneficial and detrimental, roles in health and disease and suggest the relevance of Arid5a as a potential therapeutic target.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.827611","type":"journal-article","created":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T23:50:08Z","timestamp":1642549808000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Recent Advances in the Role of Arid5a in Immune Diseases and Cancer"],"prefix":"10.3389","volume":"12","author":[{"given":"Kishan Kumar","family":"Nyati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadamitsu","family":"Kishimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev.immunol.23.021704.115806","article-title":"Interleukin-6: From Basic Science to Medicine-40 Years in Immunology","volume":"23","author":"Kishimoto","year":"2005","journal-title":"Annu Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3490765","article-title":"in a Colon Cancer Cell Line","volume":"349","author":"Legrand-Poels","year":"2000","journal-title":"Biochem J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2011.02.003","article-title":"IL-6 Signaling in Autoimmunity, Chronic Inflammation and Inflammation-Associated Cancer","volume":"22","author":"Neurath","year":"2011","journal-title":"Cytokine Growth Factor Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.10.5.2327-2334.1990","article-title":"Activation of Interleukin-6 Gene Expression Through the NF-Kappa B Transcription Factor","volume":"10","author":"Libermann","year":"1990","journal-title":"Mol Cell Biol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.21.10193","article-title":"Transcription Factors NF-IL6 and NF-Kappa B Synergistically Activate Transcription of the Inflammatory Cytokines, Interleukin 6 and Interleukin 8","volume":"90","author":"Matsusaka","year":"1993","journal-title":"Proc Natl Acad Sci USA"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxr072","article-title":"Aryl Hydrocarbon Receptor Negatively Regulates LPS-Induced IL-6 Production Through Suppression of Histamine Production in Macrophages","volume":"23","author":"Masuda","year":"2011","journal-title":"Int Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/2934","article-title":"A Novel DNA-Binding Motif Shares Structural Homology to DNA Replication and Repair Nucleases and Polymerases","volume":"5","author":"Yuan","year":"1998","journal-title":"Nat Struct Biol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.21.6084","article-title":"Solution Structure of the DNA Binding Domain From Dead Ringer, a Sequence-Specific AT-Rich Interaction Domain (ARID)","volume":"18","author":"Iwahara","year":"1999","journal-title":"EMBO J"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1023\/a:1012434510376","article-title":"1H, 13C and 15N Resonance Assignments and Secondary Structure of ADR6 DNA-Binding Domain","volume":"21","author":"Tu","year":"2001","journal-title":"J Biomol NMR"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312115200","article-title":"Structure and DNA-Binding Sites of the SWI1 AT-Rich Interaction Domain (ARID) Suggest Determinants for Sequence-Specific DNA Recognition","volume":"279","author":"Kim","year":"2004","journal-title":"J Biol Chem"},{"key":"B11","first-page":"95","article-title":"ARID Proteins: A Diverse Family of DNA Binding Proteins Implicated in the Control of Cell Growth, Differentiation, and Development","volume":"13","author":"Wilsker","year":"2002","journal-title":"Cell Growth Differ"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/s0968-0004(00)01597-8","article-title":"ARID Proteins Come in From the Desert","volume":"25","author":"Kortschak","year":"2000","journal-title":"Trends Biochem Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1042\/bj3640255","article-title":"Cloning and Characterization of hELD\/OSA1, a Novel BRG1 Interacting Protein","volume":"364","author":"Hurlstone","year":"2002","journal-title":"Biochem J"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2005.03.013","article-title":"Nomenclature of the ARID Family of DNA-Binding Proteins","volume":"86","author":"Wilsker","year":"2005","journal-title":"Genomics"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1307419110","article-title":"Arid5a Controls IL-6 mRNA Stability, Which Contributes to Elevation of IL-6 Level In Vivo","volume":"110","author":"Masuda","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151289","article-title":"Arid5a Regulates Naive CD4+ T Cell Fate Through Selective Stabilization of Stat3 mRNA","volume":"213","author":"Masuda","year":"2016","journal-title":"J Exp Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1613307113","article-title":"Arid5a Exacerbates IFN-\u03b3-Mediated Septic Shock by Stabilizing T-Bet mRNA","volume":"113","author":"Zaman","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"B18","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/eji.201747109","article-title":"Arid5a Stabilizes OX40 mRNA in Murine CD4+ T Cells by Recognizing a Stem-Loop Structure in its 3\u2032UTR","volume":"48","author":"Hanieh","year":"2018","journal-title":"Eur J Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1906712116","article-title":"Feedback Regulation of Arid5a and Ppar-\u03b32 Maintains Adipose Tissue Homeostasis","volume":"116","author":"Chalise","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"B20","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.canlet.2021.08.004","article-title":"The Novel Long Noncoding RNA AU021063, Induced by IL-6\/Arid5a Signaling, Exacerbates Breast Cancer Invasion and Metastasis by Stabilizing Trib3 and Activating the Mek\/Erk Pathway","volume":"520","author":"Nyati","year":"2021","journal-title":"Cancer Lett"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx064","article-title":"TLR4-Induced NF-\u03bab and MAPK Signaling Regulate the IL-6 mRNA Stabilizing Protein Arid5a","volume":"45","author":"Nyati","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1719921115","article-title":"Regulation of Inflammatory Responses by Dynamic Subcellular Localization of RNA-Binding Protein Arid5a","volume":"115","author":"Higa","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02790","article-title":"Arid5a Regulation and the Roles of Arid5a in the Inflammatory Response and Disease","volume":"10","author":"Nyati","year":"2019","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.01.004","article-title":"Arid5a, an RNA-Binding Protein in Immune Regulation: RNA Stability, Inflammation, and Autoimmunity","volume":"41","author":"Nyati","year":"2020","journal-title":"Trends Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aay0574","article-title":"Noncanonical STAT1 Phosphorylation Expands Its Transcriptional Activity Into Promoting LPS-Induced IL-6 and IL-12p40 Production","volume":"13","author":"Metwally","year":"2020","journal-title":"Sci Signal"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/art.38324","article-title":"AT-Rich Interactive Domain-Containing Protein 5a Functions as a Negative Regulator of Retinoic Acid Receptor-Related Orphan Nuclear Receptor \u03b3t-Induced Th17 Cell Differentiation","volume":"66","author":"Saito","year":"2014","journal-title":"Arthritis Rheumatol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1093\/intimm\/dxx004","article-title":"Arid5a-Deficient Mice are Highly Resistant to Bleomycin-Induced Lung Injury","volume":"29","author":"Dubey","year":"2017","journal-title":"Int Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz6105","article-title":"Reprogramming of Tumor-Associated Macrophages by Targeting \u03b2-Catenin\/Fosl2\/Arid5a Signaling: A Potential Treatment of Lung Cancer","volume":"6","author":"Sarode","year":"2020","journal-title":"Sci Adv"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-21-0014","article-title":"Arid5a Promotes Immune Evasion by Augmenting Tryptophan Metabolism and Chemokine Expression","volume":"9","author":"Parajuli","year":"2021","journal-title":"Cancer Immunol Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.638803","article-title":"Expression and Prognostic Value of Arid5a and its Correlation With Tumor-Infiltrating Immune Cells in Glioma","volume":"11","author":"Zhou","year":"2021","journal-title":"Front Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E10-07-0566","article-title":"Arid5a Cooperates With Sox9 to Stimulate Chondrocyte-Specific Transcription","volume":"22","author":"Amano","year":"2011","journal-title":"Mol Biol Cell"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/24.9.1695","article-title":"Repression by a Differentiation-Specific Factor of the Human Cytomegalovirus Enhancer","volume":"24","author":"Huang","year":"1996","journal-title":"Nucleic Acids Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2017.05.003","article-title":"RNA-Binding Proteins in Cancer: Old Players and New Actors","volume":"3","author":"Pereira","year":"2017","journal-title":"Trends Cancer"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-012-0179-x","article-title":"Post-Transcriptional Regulation in Cancer Progression: Microenvironmental Control of Alternative Splicing and Translation","volume":"6","author":"Jewer","year":"2012","journal-title":"J Cell Commun Signal"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0311","article-title":"Modulator Recognition Factor 1, an AT-Rich Interaction Domain Family Member, is a Novel Corepressor for Estrogen Receptor \u03b1","volume":"19","author":"Georgescu","year":"2005","journal-title":"Mol Endocrinol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/nature07924","article-title":"Zc3h12a is an RNase Essential for Controlling Immune Responses by Regulating mRNA Decay","volume":"458","author":"Matsushita","year":"2009","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2137","article-title":"The I\u03bab Kinase Complex Regulates the Stability of Cytokine-Encoding mRNA Induced by TLR-IL-1R by Controlling Degradation of REGNASE-1","volume":"12","author":"Iwasaki","year":"2011","journal-title":"Nat Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.05.002","article-title":"Cardiac Fibroblasts: At the Heart of Myocardial Remodeling","volume":"123","author":"Porter","year":"2009","journal-title":"Pharmacol Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003128200","article-title":"Interleukin-6 Family of Cytokines Mediate Angiotensin II-Induced Cardiac Hypertrophy in Rodent Cardiomyocytes","volume":"275","author":"Sano","year":"2000","journal-title":"J Biol Chem"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00904","article-title":"New Insights in Cardiac Beta-Adrenergic Signaling During Heart Failure and Aging","volume":"9","author":"de Lucia","year":"2018","journal-title":"Front Pharmacol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.101.20.2338","article-title":"Chronic Beta-Adrenergic Stimulation Induces Myocardial Proinflammatory Cytokine Expression","volume":"101","author":"Murray","year":"2000","journal-title":"Circulation"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e00590","DOI":"10.1002\/prp2.590","article-title":"\u03b22-Adrenergic Stimulation Induces Interleukin-6 by Increasing Arid5a, a Stabilizer of mRNA, Through cAMP\/PKA\/CREB Pathway in Cardiac Fibroblasts","volume":"8","author":"Tanaka","year":"2020","journal-title":"Pharmacol Res Perspect"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-378653","article-title":"Essentials of Th17 Cell Commitment and Plasticity","volume":"121","author":"Muranski","year":"2013","journal-title":"Blood"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e4","DOI":"10.1038\/cti.2013.2","article-title":"Interleukin-6: A New Therapeutic Target in Systemic Sclerosis","volume":"2","author":"O\u2019Reilly","year":"2013","journal-title":"Clin Transl Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.92","article-title":"Targeting Th17 Cells in Immune Diseases","volume":"24","author":"Dong","year":"2014","journal-title":"Cell Res"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.03.011","article-title":"CD5: A New Partner for IL-6","volume":"44","author":"Masuda","year":"2016","journal-title":"Immunity"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.04.029","article-title":"Regnase-1 and Roquin Regulate a Common Element in Inflammatory mRNAs by Spatiotemporally Distinct Mechanisms","volume":"161","author":"Mino","year":"2015","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aat4617","article-title":"IL-17 Integrates Multiple Self-Reinforcing, Feed-Forward Mechanisms Through the RNA Binding Protein Arid5a","volume":"11","author":"Amatya","year":"2018","journal-title":"Sci Signal"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1172\/JCI151627","article-title":"RNA-Binding Proteins of COSMIC Importance in Cancer","volume":"131","author":"Choi","year":"2021","journal-title":"J Clin Invest"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0095","article-title":"Tumoral Immune Resistance Mediated by Enzymes That Degrade Tryptophan","volume":"3","author":"van Baren","year":"2015","journal-title":"Cancer Immunol Res"},{"key":"B51","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1158\/2326-6066.CIR-21-0432","article-title":"Arid5a: A Missing Link Between EMT and Tumoral Immune Resistance","volume":"9","author":"van den Eynde","year":"2021","journal-title":"Cancer Immunol Res"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-1331","article-title":"Indoleamine 2,3-Dioxygenase Expression in Human Cancers: Clinical and Immunologic Perspectives","volume":"17","author":"Godin-Ethier","year":"2011","journal-title":"Clin Cancer Res"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20130066","article-title":"Indoleamine 2,3-Dioxygenase is a Critical Resistance Mechanism in Antitumor T Cell Immunotherapy Targeting CTLA-4","volume":"210","author":"Holmgaard","year":"2013","journal-title":"J Exp Med"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2019.11.014","article-title":"Chemokines and Their Receptors Promoting the Recruitment of Myeloid-Derived Suppressor Cells Into the Tumor","volume":"117","author":"Li","year":"2020","journal-title":"Mol Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.49","article-title":"Chemokines in the Cancer Microenvironment and Their Relevance in Cancer Immunotherapy","volume":"17","author":"Nagarsheth","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1089\/jamp.2009.0775","article-title":"Acute Lung Injury: Epidemiology, Pathogenesis, and Treatment","volume":"23","author":"Johnson","year":"2010","journal-title":"J Aerosol Med Pulm Drug Deliv"},{"key":"B57","doi-asserted-by":"publisher","first-page":"43","DOI":"10.4103\/0974-2700.58663","article-title":"Acute Lung Injury and Acute Respiratory Distress Syndrome","volume":"3","author":"Ragaller","year":"2010","journal-title":"J Emerg Trauma Shock"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1086\/675991","article-title":"Pleiotropic Effects of Interleukin-6 in a \u201cTwo-Hit\u201d Murine Model of Acute Respiratory Distress Syndrome","volume":"4","author":"Goldman","year":"2014","journal-title":"Pulm Circ"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0299OC","article-title":"Role of Interleukin-6 in Bleomycin-Induced Lung Inflammatory Changes in Mice","volume":"38","author":"Saito","year":"2008","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1146\/annurev.iy.11.040193.003035","article-title":"The Molecular Cell Biology of Interferon-Gamma and its Receptor","volume":"11","author":"Farrar","year":"1993","journal-title":"Annu Rev Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(00)80702-3","article-title":"A Novel Transcription Factor, T-Bet, Directs Th1 Lineage Commitment","volume":"100","author":"Szabo","year":"2000","journal-title":"Cell"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1126\/science.1065543","article-title":"Distinct Effects of T-Bet in TH1 Lineage Commitment and IFN-Gamma Production in CD4 and CD8 T Cells","volume":"295","author":"Szabo","year":"2002","journal-title":"Science"},{"key":"B63","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/ni.2059","article-title":"T-Bet in Disease","volume":"12","author":"Lazarevic","year":"2011","journal-title":"Nat Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/nri3536","article-title":"T-Bet: A Bridge Between Innate and Adaptive Immunity","volume":"13","author":"Lazarevic","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.12.007","article-title":"Exercise-Induced Changes in Visceral Adipose Tissue Mass are Regulated by IL-6 Signaling: A Randomized Controlled Trial","volume":"29","author":"Wedell-Neergaard","year":"2019","journal-title":"Cell Metab"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3159","article-title":"Ppar\u03b3 Signaling and Metabolism: The Good, the Bad and the Future","volume":"19","author":"Ahmadian","year":"2013","journal-title":"Nat Med"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/j.celrep.2018.09.086","article-title":"Sox9-Meis1 Inactivation is Required for Adipogenesis, Advancing Pref-1(+) to PDGFRalpha(+) Cells","volume":"25","author":"Gulyaeva","year":"2018","journal-title":"Cell Rep"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.10.004","article-title":"T Follicular Helper Cell Differentiation, Function, and Roles in Disease","volume":"41","author":"Crotty","year":"2014","journal-title":"Immunity"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.7.4313","article-title":"Cutting Edge: An In Vivo Requirement for STAT3 Signaling in Th17 Development and Th17-Dependent Autoimmunity","volume":"179","author":"Harris","year":"2007","journal-title":"J Immunol"},{"key":"B70","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/icb.2013.55","article-title":"Human T Follicular Helper (Tfh) Cells and Disease","volume":"92","author":"Ma","year":"2014","journal-title":"Immunol Cell Biol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/nm0296-183","article-title":"Selective Depletion of Myelin Reactive T Cells With the Anti-OX40 Antibody Ameliorates Autoimmune Encephalomyelitis","volume":"2","author":"Weinberg","year":"1996","journal-title":"Nat Med"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/s1471-4906(01)02127-5","article-title":"OX40: Targeted Immunotherapy Implications for Tempering Autoimmunity and Enhancing Vaccines","volume":"23","author":"Weinberg","year":"2002","journal-title":"Trends Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.253500","article-title":"STAT3 Protein Promotes T-Cell Survival and Inhibits Interleukin-2 Production Through Up-Regulation of Class O Forkhead Transcription Factors","volume":"286","author":"Oh","year":"2011","journal-title":"J Biol Chem"},{"key":"B74","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"B75","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21551","article-title":"Cancer Statistics, 2019","volume":"69","author":"Siegel","year":"2019","journal-title":"CA Cancer J Clin"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0830997100","article-title":"Biologic Activity of Cytotoxic T Lymphocyte-Associated Antigen 4 Antibody Blockade in Previously Vaccinated Metastatic Melanoma and Ovarian Carcinoma Patients","volume":"100","author":"Hodi","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1533209100","article-title":"Cancer Regression and Autoimmunity Induced by Cytotoxic T Lymphocyte-Associated Antigen 4 Blockade in Patients With Metastatic Melanoma","volume":"100","author":"Phan","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"B78","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s40425-018-0349-3","article-title":"Current Landscape and Future of Dual Anti-CTLA4 and PD-1\/PD-L1 Blockade Immunotherapy in Cancer; Lessons Learned From Clinical Trials With Melanoma and Non-Small Cell Lung Cancer (NSCLC)","volume":"6","author":"Chae","year":"2018","journal-title":"J Immunother Cancer"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00086","article-title":"Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations","volume":"8","author":"Seidel","year":"2018","journal-title":"Front Oncol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.immuni.2014.06.008","article-title":"Macrophage Activation and Polarization: Nomenclature and Experimental Guidelines","volume":"41","author":"Murray","year":"2014","journal-title":"Immunity"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.1.342","article-title":"Macrophages Sequentially Change Their Functional Phenotype in Response to Changes in Microenvironmental Influences","volume":"175","author":"Stout","year":"2005","journal-title":"J Immunol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.009","article-title":"Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations Across Individuals and Species","volume":"50","author":"Zilionis","year":"2019","journal-title":"Immunity"},{"key":"B83","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer Statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J Clin"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.3.837","article-title":"Erythropoietin-Independent Erythrocyte Production: Signals Through Gp130 and C-Kit Dramatically Promote Erythropoiesis From Human CD34+ Cells","volume":"183","author":"Sui","year":"1996","journal-title":"J Exp Med"},{"key":"B85","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1093\/intimm\/8.4.595","article-title":"The Soluble Form of the IL-6 Receptor (sIL-6R Alpha) is a Potent Growth Factor for AIDS-Associated Kaposi\u2019s Sarcoma (KS) Cells; the Soluble Form of Gp130 Iis Antagonistic for sIL-6R Alpha-Induced AIDS-KS Cell Growth","volume":"8","author":"Murakami-Mori","year":"1996","journal-title":"Int Immunol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/34.4.321","article-title":"Interleukin-6 (IL-6) Induces the Proliferation of Synovial Fibroblastic Cells in the Presence of Soluble IL-6 Receptor","volume":"34","author":"Mihara","year":"1995","journal-title":"Br J Rheumatol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2016.12.005","article-title":"Transcriptional and Post-Transcriptional Gene Regulation by Long non-Coding RNA","volume":"15","author":"Dykes","year":"2017","journal-title":"Genomics Proteomics Bioinf"},{"key":"B88","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.molimm.2019.04.011","article-title":"Long non-Coding RNA: Classification, Biogenesis and Functions in Blood Cells","volume":"112","author":"Dahariya","year":"2019","journal-title":"Mol Immunol"},{"key":"B89","doi-asserted-by":"publisher","first-page":"8316","DOI":"10.1038\/s41598-020-65421-2","article-title":"In Silico Identification of MAPK14-Related lncRNAs and Assessment of Their Expression in Breast Cancer Samples","volume":"10","author":"Dashti","year":"2020","journal-title":"Sci Rep"},{"key":"B90","article-title":"A Novel Positive Feedback Regulation Between Long Noncoding RNA UICC and IL-6\/STAT3 Signaling Promotes Cervical Cancer Progression","volume":"8","author":"Su","year":"2018","journal-title":"Am J Cancer Res"},{"key":"B91","doi-asserted-by":"publisher","first-page":"5720","DOI":"10.1038\/s41467-019-13700-6","article-title":"TRIB3 Supports Breast Cancer Stemness by Suppressing FOXO1 Degradation and Enhancing SOX2 Transcription","volume":"10","author":"Yu","year":"2019","journal-title":"Nat Commun"},{"key":"B92","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1186\/s12935-020-01509-z","article-title":"Down-Regulation of TRIB3 Inhibits the Progression of Ovarian Cancer via MEK\/ERK Signaling Pathway","volume":"20","author":"Wang","year":"2020","journal-title":"Canc Cell Int"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.082875","article-title":"TRB3 Interacts With SMAD3 Promoting Tumor Cell Migration and Invasion","volume":"124","author":"Hua","year":"2011","journal-title":"J Cell Sci"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202489","article-title":"Expression and Prognostic Values of ARID Family Members in Breast Cancer","volume":"13","author":"Zhang","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B95","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.immuni.2019.12.018","article-title":"Tumor Immunology and Tumor Evolution: Intertwined Histories","volume":"52","author":"Galon","year":"2020","journal-title":"Immunity"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cancerbio-030617-050606","article-title":"Mechanisms of Tumor Cell\u2013Intrinsic Immune Evasion","volume":"2","author":"Spranger","year":"2018","journal-title":"Annu Rev Cancer Biol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.03.008","article-title":"The Immune Revolution: A Case for Priming, Not Checkpoint","volume":"33","author":"Vonderheide","year":"2018","journal-title":"Cancer Cell"},{"key":"B99","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/s41573-018-0007-y","article-title":"Approaches to Treat Immune Hot, Altered and Cold Tumours With Combination Immunotherapies","volume":"18","author":"Galon","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"B100","doi-asserted-by":"publisher","first-page":"48","DOI":"10.4103\/1008-682X.132780","article-title":"Prostate Cancer in East Asia: Evolving Trend Over the Last Decade","volume":"17","author":"Zhu","year":"2015","journal-title":"Asian J Androl"},{"key":"B101","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/s41598-019-57056-9","article-title":"Impact of Advanced Radiotherapy Techniques and Dose Intensification on Toxicity of Salvage Radiotherapy After Radical Prostatectomy","volume":"10","author":"Tomita","year":"2020","journal-title":"Sci Rep"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39498.525706.AD","article-title":"Diagnosis and Treatment of Prostate Cancer: Summary of NICE Guidance","volume":"336","author":"Graham","year":"2008","journal-title":"BMJ"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2014.72","article-title":"Evolution of Androgen Receptor Targeted Therapy for Advanced Prostate Cancer","volume":"11","author":"Wong","year":"2014","journal-title":"Nat Rev Clin Oncol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5098-7","article-title":"Role of Interleukin-6 in Cancer Progression and Therapeutic Resistance","volume":"37","author":"Kumari","year":"2016","journal-title":"Tumour Biol"},{"key":"B105","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.canlet.2016.02.048","article-title":"Cancer Development, Chemoresistance, Epithelial to Mesenchymal Transition and Stem Cells: A Snapshot of IL-6 Mediated Involvement","volume":"375","author":"Bharti","year":"2016","journal-title":"Cancer Lett"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1111\/bju.12452","article-title":"Inflammation and Prostate Cancer: The Role of Interleukin 6 (IL-6)","volume":"113","author":"Nguyen","year":"2014","journal-title":"BJU Int"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/s0090-4295(01)01405-4","article-title":"Plasma Levels of Interleukin-6 and its Soluble Receptor are Associated With Prostate Cancer Progression and Metastasis","volume":"58","author":"Shariat","year":"2001","journal-title":"Urology"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-1560","article-title":"The Prognostic Significance of Plasma Interleukin-6 Levels in Patients With Metastatic Hormone-Refractory Prostate Cancer: Results From Cancer and Leukemia Group B 9480","volume":"11","author":"George","year":"2005","journal-title":"Clin Cancer Res"},{"key":"B109","article-title":"Interleukin-6 Promotes Androgen-Independent Growth in LNCaP Human Prostate Cancer Cells","volume":"9","author":"Lee","year":"2003","journal-title":"Clin Cancer Res"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-13-0605","article-title":"Pharmacologic Suppression of JAK1\/2 by JAK1\/2 Inhibitor AZD1480 Potently Inhibits IL-6-Induced Experimental Prostate Cancer Metastases Formation","volume":"13","author":"Gu","year":"2014","journal-title":"Mol Cancer Ther"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26639","article-title":"Interleukin-6 Induced Overexpression of Valosin-Containing Protein (VCP)\/p97 is Associated With Androgen-Independent Prostate Cancer (AIPC) Progression","volume":"233","author":"Duscharla","year":"2018","journal-title":"J Cell Physiol"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-18-0508","article-title":"The STAT3 Inhibitor Galiellalactone Reduces IL6-Mediated AR Activity in Benign and Malignant Prostate Models","volume":"17","author":"Handle","year":"2018","journal-title":"Mol Cancer Ther"},{"key":"B113","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/pros.24251","article-title":"AT-Rich Interaction Domain 5A Regulates the Transcription of Interleukin-6 Gene in Prostate Cancer Cells","volume":"82","author":"Ikeuchi","year":"2021","journal-title":"Prostate"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2017-4489","article-title":"Knockdown Arid5a Suppresses Proliferation of LNCaP Prostate Cancer Cell Through the Inhibition of Global Protein Synthesis","volume":"77","author":"Sun","year":"2017","journal-title":"Proc Am Assoc Cancer Res Annu Meet; Cancer Res"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.31039","article-title":"Isocitrate Dehydrogenase-Mutant Glioma: Evolving Clinical and Therapeutic Implications","volume":"123","author":"Miller","year":"2017","journal-title":"Cancer"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2018.1548935","article-title":"The Clinical Use of Idh1 and Idh2 Mutations in Gliomas","volume":"18","author":"Picca","year":"2018","journal-title":"Expert Rev Mol Diagn"},{"key":"B117","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.semcancer.2019.10.018","article-title":"Current State and Future Perspective of Drug Repurposing in Malignant Glioma","volume":"68","author":"Siegelin","year":"2021","journal-title":"Semin Cancer Biol"},{"key":"B118","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3390\/cancers12010013","article-title":"Overexpression of Psat1 Gene is a Favorable Prognostic Marker in Lower-Grade Gliomas and Predicts a Favorable Outcome in Patients With Idh1 Mutations and Chromosome 1p19q Codeletion","volume":"12","author":"Huang","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.7150\/jca.41123","article-title":"Prognostic Significance of Age-Related Genes in Patients With Lower Grade Glioma","volume":"11","author":"Wang","year":"2020","journal-title":"J Cancer"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2019.08.117","article-title":"Galectin-9: A Predictive Biomarker Negatively Regulating Immune Response in Glioma Patients","volume":"132","author":"Liang","year":"2019","journal-title":"World Neurosurg"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-017-2379-y","article-title":"Molecular Markers in Glioma","volume":"134","author":"Ludwig","year":"2017","journal-title":"J Neurooncol"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1545-1","article-title":"The 2016 World Health Organization Classification of Tumors of the Central Nervous System: A Summary","volume":"131","author":"Louis","year":"2016","journal-title":"Acta Neuropathol"},{"key":"B123","doi-asserted-by":"publisher","first-page":"15017","DOI":"10.1038\/nrdp.2015.17","article-title":"Glioma","volume":"1","author":"Weller","year":"2015","journal-title":"Nat Rev Dis Primers"},{"key":"B124","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3892\/ijo.2017.4184","article-title":"AJAP1 Expression Modulates Glioma Cell Motility and Correlates With Tumor Growth and Survival","volume":"52","author":"Di","year":"2018","journal-title":"Int J Oncol"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2014.1","article-title":"Interleukin 6 Downregulates P53 Expression and Activity by Stimulating Ribosome Biogenesis: A New Pathway Connecting Inflammation to Cancer","volume":"33","author":"Brighenti","year":"2014","journal-title":"Oncogene"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.17.7432-7440.2005","article-title":"Role of Stat3 in Regulating P53 Expression and Function","volume":"25","author":"Niu","year":"2005","journal-title":"Mol Cell Biol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0224","article-title":"Dual Faces of Ifn\u03b3 in Cancer Progression: A Role of PD-L1 Induction in the Determination of Pro- and Antitumor Immunity","volume":"22","author":"Mandai","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27782","article-title":"CD8+ Cytotoxic T Lymphocytes in Cancer Immunotherapy: A Review","volume":"234","author":"Farhood","year":"2019","journal-title":"J Cell Physiol"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1038\/nri2958","article-title":"Genomic Views of STAT Function in CD4+ T Helper Cell Differentiation","volume":"11","author":"O\u2019Shea","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3153","article-title":"IL-6 as a Keystone Cytokine in Health and Disease","volume":"16","author":"Hunter","year":"2015","journal-title":"Nat Immunol"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.037","article-title":"Emerging Biological Principles of Metastasis","volume":"168","author":"Lambert","year":"2017","journal-title":"Cell"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.015","article-title":"Endothelial Cells are Central Orchestrators of Cytokine Amplification During Influenza Virus Infection","volume":"146","author":"Teijaro","year":"2011","journal-title":"Cell"},{"key":"B133","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/nature12118","article-title":"The TLR4 Antagonist Eritoran Protects Mice From Lethal Influenza Infection","volume":"497","author":"Shirey","year":"2013","journal-title":"Nature"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.1.503","article-title":"Protective Effects of IL-6 Blockade in Sepsis are Linked to Reduced C5a Receptor Expression","volume":"170","author":"Riedemann","year":"2003","journal-title":"J Immunol"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.5.2751-2757.2005","article-title":"Role of Interleukin-6 in Mortality From and Physiologic Response to Sepsis","volume":"73","author":"Remick","year":"2005","journal-title":"Infect Immun"},{"key":"B136","doi-asserted-by":"publisher","first-page":"E3528","DOI":"10.3390\/ijms19113528","article-title":"The Two-Faced Cytokine IL-6 in Host Defense and Diseases","volume":"19","author":"Narazaki","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B137","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s11060-008-9590-9","article-title":"Blockage of the STAT3 Signaling Pathway With a Decoy Oligonucleotide Suppresses Growth of Human Malignant Glioma Cells","volume":"89","author":"Gu","year":"2008","journal-title":"J Neurooncol"},{"key":"B138","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1093\/neuonc\/nos302","article-title":"On-Target JAK2\/STAT3 Inhibition Slows Disease Progression in Orthotopic Xenografts of Human Glioblastoma Brain Tumor Stem Cells","volume":"15","author":"Stechishin","year":"2013","journal-title":"Neuro Oncol"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2010.06.025","article-title":"Human Uveal Melanoma Cells Inhibit the Immunostimulatory Function of Dendritic Cells","volume":"91","author":"Ma","year":"2010","journal-title":"Exp Eye Res"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7458238","article-title":"STAT Family Protein Expression and Phosphorylation State During moDC Development Is Altered by Platinum-Based Chemotherapeutics","volume":"2019","author":"de Haas","year":"2019","journal-title":"J Immunol Res"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2253","article-title":"Multifunctional Effects of a Small Molecule STAT3 Inhibitor on NASH and Hepatocellular Carcinoma in Mice","volume":"23","author":"Jung","year":"2017","journal-title":"Clin Cancer Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.827611\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T23:50:13Z","timestamp":1642549813000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.827611\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,19]]},"references-count":141,"alternative-id":["10.3389\/fimmu.2021.827611"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.827611","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,19]]},"article-number":"827611"}}