{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:59:54Z","timestamp":1793915994548,"version":"4.8.0"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008513","name":"Thomas Jefferson University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008513","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>FDA-approved chimeric antigen receptor (CAR)-expressing T cell therapies (CARTs) have revolutionized the treatment of blood cancers. Yet none have been successful for \"solid\" tumors, such as colorectal cancer (CRC), the 2nd leading cause of cancer deaths. Guanylyl cyclase C (GUCY2C) has emerged as a clinical-stage target for CART and bispecific T-cell engager (BiTE) therapies in CRC. IFN\u03b3 has been canonically recognized as beneficial for the effector functions of T cells by enhancing antigen processing and HLA presentation and is essential for CART targeting of solid malignancies by inducing adhesion molecule expression for synapse stabilization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using\n                      <jats:italic>in vitro<\/jats:italic>\n                      co-culture systems, conditioned media experiments, cytokine screening, pharmacologic inhibition, CRISPR-Cas9 knockout, and transcriptomic analyses, we investigated mechanisms of GUCY2C antigen loss in CRC cells exposed to activated CART cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a novel antigen loss mechanism that limits the efficacy of CART in CRC, in which IFN\u03b3 secreted by activated CART cells causes bystander cancer cells to lose GUCY2C. This previously unexplored antigen loss mechanism is mediated through IFN\u03b3 receptor, JAK, and cellular stress signaling pathways. This mechanism of antigen loss can be rescued with anti-IFN\u03b3 neutralizing antibody, the JAK inhibitor ruxolitinib, or 4-phenylbutyrate (an ER stress reliever).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We revealed a negative effect of IFN\u03b3 that uniquely interferes with immunotherapies targeting native surface antigens, such as CART and BiTE therapies, which may be reversed by disrupting stress signaling pathways to enhance solid tumor CART and BiTE immunotherapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1772472","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:13:44Z","timestamp":1773756824000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["IFN\u03b3-induced antigen loss in chimeric antigen receptor-T cell therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Miao","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramkrishna","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor R.","family":"Baybutt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyang","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwatobiloba","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison S.","family":"Doermann","sequence":"additional","affiliation":[{"name":"Department of Surgery, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross E.","family":"Staudt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott A.","family":"Waldman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam E.","family":"Snook","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.985","article-title":"Rapid advances in immunotherapy to treat cancer","volume":"103","author":"McCune","year":"2018","journal-title":"Clin Pharmacol Ther"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201745172","article-title":"The fourth pillar: Despite some setbacks in the clinic, immunotherapy has made notable progress toward becoming an additional therapeutic option against cancer","volume":"18","author":"Hunter","year":"2017","journal-title":"EMBO Rep"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30422-9","article-title":"Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study","volume":"18","author":"Overman","year":"2017","journal-title":"Lancet Oncol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"TPS3635","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS3635","article-title":"Phase 2\/3, randomized, open-label study of an individualized neoantigen vaccine (self-amplifying mRNA and adenoviral vectors) plus immune checkpoint blockade as maintenance for patients with newly diagnosed metastatic colorectal cancer (GRANITE)","volume":"40","author":"Hecht","year":"2022","journal-title":"JCO"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019-0129","article-title":"Safety of nivolumab plus low-dose ipilimumab in previously treated microsatellite instability-high\/mismatch repair-deficient metastatic colorectal cancer","volume":"24","author":"Morse","year":"2019","journal-title":"Oncologist"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12459","article-title":"Clinical pharmacology and translational aspects of bispecific antibodies","volume":"10","author":"Trivedi","year":"2017","journal-title":"Clin Transl Sci"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0547","article-title":"Bispecific T-cell engaging antibodies for cancer therapy","volume":"69","author":"Baeuerle","year":"2009","journal-title":"Cancer Res"},{"key":"B8","first-page":"12","article-title":"Symmetry breaking: bispecific antibodies, the beginnings, and 50 years on","volume":"12","author":"Riethm\u00fcller","year":"2012","journal-title":"Cancer Immun"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.07.004","article-title":"Long-duration complete remissions of diffuse large B cell lymphoma after anti-CD19 chimeric antigen receptor T cell therapy","volume":"25","author":"Kochenderfer","year":"2017","journal-title":"Mol Ther"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00754-1","article-title":"Long-term outcomes following CAR T cell therapy: what we know so far","volume":"20","author":"Cappell","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2018.77.8084","article-title":"T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma","volume":"36","author":"Brudno","year":"2018","journal-title":"J Clin Oncol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1080\/23808993.2025.2560303","article-title":"Immunotherapy for precision medicine in colorectal cancer","volume":"10","author":"Cao","year":"2025","journal-title":"Expert Rev Precis Med Drug Dev"},{"key":"B13","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s13287-022-02719-0","article-title":"Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress","volume":"13","author":"Budi","year":"2022","journal-title":"Stem Cell Res Ther"},{"key":"B14","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1056\/NEJMra043186","article-title":"Trastuzumab--mechanism of action and use in clinical practice","volume":"357","author":"Hudis","year":"2007","journal-title":"N Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00579-0","article-title":"Targeting HER2-positive breast cancer: advances and future directions","volume":"22","author":"Swain","year":"2023","journal-title":"Nat Rev Drug Discov"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61121-X","article-title":"Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial","volume":"376","author":"Bang","year":"2010","journal-title":"Lancet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3332","DOI":"10.1038\/s41467-023-38032-4","article-title":"Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer","volume":"14","author":"Yoshino","year":"2023","journal-title":"Nat Commun"},{"key":"B18","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1200\/JCO.23.02005","article-title":"Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing solid tumors: primary results from the DESTINY-panTumor02 phase II trial","volume":"42","author":"Meric-Bernstam","year":"2024","journal-title":"J Clin Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.24","article-title":"Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2","volume":"18","author":"Morgan","year":"2010","journal-title":"Mol Ther"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.0225","article-title":"Human epidermal growth factor receptor 2 (HER2) -specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma","volume":"33","author":"Ahmed","year":"2015","journal-title":"J Clin Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-024-00749-6","article-title":"Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial","volume":"5","author":"Hegde","year":"2024","journal-title":"Nat Cancer"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0184","article-title":"HER2-specific chimeric antigen receptor-modified virus-specific T cells for progressive glioblastoma: A phase 1 dose-escalation trial","volume":"3","author":"Ahmed","year":"2017","journal-title":"JAMA Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.3514","article-title":"Phase I trial of hypoxia-responsive CEA CAR-T cell therapy in patients with heavily pretreated solid tumor via intraperitoneal or intravenous transfusion","volume":"42","author":"Zhang","year":"2024","journal-title":"JCO"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100227","article-title":"Hypoxia-sensing CAR T cells provide safety and efficacy in treating solid tumors","volume":"2","author":"Kosti","year":"2021","journal-title":"Cell Rep Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-022-00344-7","article-title":"Potent suppression of neuroendocrine tumors and gastrointestinal cancers by CDH17CAR T cells without toxicity to normal tissues","volume":"3","author":"Feng","year":"2022","journal-title":"Nat Cancer"},{"key":"B26","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/s40425-019-0576-2","article-title":"Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients","volume":"7","author":"Snook","year":"2019","journal-title":"J Immunother Cancer"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-3275","article-title":"A novel GUCY2C-CD3 T-cell engaging bispecific construct (PF-07062119) for the treatment of gastrointestinal cancers","volume":"26","author":"Mathur","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-16-0362","article-title":"Human GUCY2C-targeted chimeric antigen receptor (CAR)-expressing T cells eliminate colorectal cancer metastases","volume":"6","author":"Magee","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e1227897","DOI":"10.1080\/2162402X.2016.1227897","article-title":"GUCY2C-directed CAR-T cells oppose colorectal cancer metastases without autoimmunity","volume":"5","author":"Magee","year":"2016","journal-title":"Oncoimmunology"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2024.2398801","article-title":"CD8\u03b1 Structural domains enhance GUCY2C CAR-T cell efficacy","volume":"25","author":"Baybutt","year":"2024","journal-title":"Cancer Biol Ther"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.2518","article-title":"Phase I study of GUCY2C CAR-T therapy IM96 in patients with metastatic colorectal cancer","volume":"42","author":"Qi","year":"2024","journal-title":"JCO"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.4_suppl.175","article-title":"A phase 1 dose-escalation study of GCC19CART: A novel CAR T-cell therapy for metastatic colorectal cancer in the United States","volume":"43","author":"Keenan","year":"2025","journal-title":"JCO"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.3891","article-title":"Chimeric antigen receptor T cells targeting CD19 and GCC in metastatic colorectal cancer: A nonrandomized clinical trial","volume":"10","author":"Chen","year":"2024","journal-title":"JAMA Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2023.41.16_suppl.3559","article-title":"Novel GUCY2C targeting CAR-T therapy: Efficacy in advanced colorectal cancer","volume":"41","author":"Zhang","year":"2023","journal-title":"JCO"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-1020","article-title":"Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy","volume":"5","author":"Sotillo","year":"2015","journal-title":"Cancer Discov"},{"key":"B36","doi-asserted-by":"publisher","first-page":"5570","DOI":"10.1038\/s41467-022-31818-y","article-title":"High-throughput mutagenesis identifies mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance","volume":"13","author":"Cort\u00e9s-L\u00f3pez","year":"2022","journal-title":"Nat Commun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01245-5","article-title":"Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with multiple myeloma","volume":"27","author":"Da Vi\u00e0","year":"2021","journal-title":"Nat Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1038\/s41467-021-21177-5","article-title":"Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma","volume":"12","author":"Samur","year":"2021","journal-title":"Nat Commun"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0442","article-title":"Tumor antigen escape from CAR T-cell therapy","volume":"8","author":"Majzner","year":"2018","journal-title":"Cancer Discov"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001150","article-title":"Point mutation in CD19 facilitates immune escape of B cell lymphoma from CAR-T cell therapy","volume":"8","author":"Zhang","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa0984","article-title":"A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma","volume":"9","author":"O\u2019Rourke","year":"2017","journal-title":"Sci Transl Med"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1610497","article-title":"Regression of glioblastoma after chimeric antigen receptor T-cell therapy","volume":"375","author":"Brown","year":"2016","journal-title":"N Engl J Med"},{"key":"B43","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1053\/j.gastro.2018.03.029","article-title":"Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial","volume":"155","author":"Beatty","year":"2018","journal-title":"Gastroenterology"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nri1604","article-title":"Mechanisms of type-I- and type-II-interferon-mediated signalling","volume":"5","author":"Platanias","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"B45","first-page":"1","article-title":"The janus protein tyrosine kinase family and its role in cytokine signaling","volume-title":"Advances in immunology","author":"Ihle","year":"1995"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.563","article-title":"The IFN gamma receptor: a paradigm for cytokine receptor signaling","volume":"15","author":"Bach","year":"1997","journal-title":"Annu Rev Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1126\/science.8197455","article-title":"Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins","volume":"264","author":"Darnell","year":"1994","journal-title":"Science"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1002028","article-title":"Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis","volume":"363","author":"Verstovsek","year":"2010","journal-title":"N Engl J Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-3145","article-title":"Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis","volume":"18","author":"Mascarenhas","year":"2012","journal-title":"Clin Cancer Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/nature07203","article-title":"From endoplasmic-reticulum stress to the inflammatory response","volume":"454","author":"Zhang","year":"2008","journal-title":"Nature"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1523-3","article-title":"Pro-inflammatory cytokines induce cell death, inflammatory responses, and endoplasmic reticulum stress in human iPSC-derived beta cells","volume":"11","author":"Demine","year":"2020","journal-title":"Stem Cell Res Ther"},{"key":"B52","doi-asserted-by":"publisher","first-page":"8100","DOI":"10.1038\/s41598-017-08722-3","article-title":"Neuroinflammation alters cellular proteostasis by producing endoplasmic reticulum stress, autophagy activation and disrupting ERAD activation","volume":"7","author":"Pintado","year":"2017","journal-title":"Sci Rep"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/cells9102183","article-title":"Proteostasis disturbances and inflammation in neurodegenerative diseases","volume":"9","author":"Sonninen","year":"2020","journal-title":"Cells"},{"key":"B54","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1038\/s41419-019-1729-4","article-title":"Expression of UPR effector proteins ATF6 and XBP1 reduce colorectal cancer cell proliferation and stemness by activating PERK signaling","volume":"10","author":"Spaan","year":"2019","journal-title":"Cell Death Dis"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0250-z","article-title":"Mechanisms, regulation and functions of the unfolded protein response","volume":"21","author":"Hetz","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/nrm3270","article-title":"The unfolded protein response: controlling cell fate decisions under ER stress and beyond","volume":"13","author":"Hetz","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1128\/MCB.00911-15","article-title":"C\/EBP\u03b3 Is a critical regulator of cellular stress response networks through heterodimerization with ATF4","volume":"36","author":"Huggins","year":"2015","journal-title":"Mol Cell Biol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2014.12.019","article-title":"Tunicamycin-induced unfolded protein response in the developing mouse brain","volume":"283","author":"Wang","year":"2015","journal-title":"Toxicol Appl Pharmacol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.170148","article-title":"The unfolded protein response links ER stress to cancer-associated thrombosis","volume":"8","author":"Muse","year":"2023","journal-title":"JCI Insight"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1002\/elps.201100565","article-title":"Proteome analysis of tunicamycin-induced ER stress","volume":"33","author":"Bull","year":"2012","journal-title":"Electrophoresis"},{"key":"B61","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s10238-013-0269-y","article-title":"Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1","volume":"15","author":"Jiang","year":"2015","journal-title":"Clin Exp Med"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvae048","article-title":"Neurodegenerative diseases associated with the disruption of proteostasis and their therapeutic strategies using chemical chaperones","volume":"176","author":"Sugiyama","year":"2024","journal-title":"J Biochem"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242115816","article-title":"Chemical chaperone 4-PBA mitigates tumor necrosis factor alpha-induced endoplasmic reticulum stress in human airway smooth muscle","volume":"24","author":"Delmotte","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.08.014","article-title":"Chemical chaperone 4-phenylbutyric acid alleviates the aggregation of human familial pulmonary fibrosis-related mutant SP-A2 protein in part through effects on GRP78","volume":"1864","author":"Jiang","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1186\/2045-3701-4-75","article-title":"Chemical chaperone 4-phenylbutyrate prevents endoplasmic reticulum stress induced by T17M rhodopsin","volume":"4","author":"Jiang","year":"2014","journal-title":"Cell Biosci"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0184-6","article-title":"Mechanisms of resistance to CAR T cell therapy","volume":"16","author":"Shah","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(00)80483-5","article-title":"Evidence that a single peptide-MHC complex on a target cell can elicit a cytolytic T cell response","volume":"4","author":"Sykulev","year":"1996","journal-title":"Immunity"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700236","article-title":"Comparison of T cell activities mediated by human tcrs and cars that use the same recognition domains","volume":"200","author":"Harris","year":"2018","journal-title":"J Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102353","article-title":"CAR-T cells in solid tumors: Challenges and breakthroughs","volume":"6","author":"Escobar","year":"2025","journal-title":"Cell Rep Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01207-0","article-title":"CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors","volume":"21","author":"Peng","year":"2024","journal-title":"Cell Mol Immunol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.025","article-title":"Shared and distinct functions of type I and type III interferons","volume":"50","author":"Lazear","year":"2019","journal-title":"Immunity"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.13.7556","article-title":"Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice","volume":"95","author":"Kaplan","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1038\/35074122","article-title":"IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity","volume":"410","author":"Shankaran","year":"2001","journal-title":"Nature"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(90)90437-p","article-title":"Interferon-gamma: mechanism of action and therapeutic potential","volume":"40","author":"Billiau","year":"1990","journal-title":"Biochem Pharmacol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2024-201300","article-title":"A single-cell transcriptomic atlas of cytokine storm in CAR-T therapy, COVID-19, and SLE","volume":"144","author":"Li","year":"2024","journal-title":"Blood"},{"key":"B76","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s00281-024-01013-w","article-title":"Riding the storm: managing cytokine-related toxicities in CAR-T cell therapy","volume":"46","author":"Hughes","year":"2024","journal-title":"Semin Immunopathol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04585-5","article-title":"CAR T cell killing requires the IFN\u03b3R pathway in solid but not liquid tumours","volume":"604","author":"Larson","year":"2022","journal-title":"Nature"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9440(10)64871-7","article-title":"Interferon-gamma reduces melanosomal antigen expression and recognition of melanoma cells by cytotoxic T cells","volume":"160","author":"Le Poole","year":"2002","journal-title":"Am J Pathol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.10.5502","article-title":"IFN-gamma can promote tumor evasion of the immune system in vivo by down-regulating cellular levels of an endogenous tumor antigen","volume":"165","author":"Beatty","year":"2000","journal-title":"J Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2020.12.037","article-title":"Th1 cytokine interferon gamma improves response in HER2 breast cancer by modulating the ubiquitin proteasomal pathway","volume":"29","author":"Jia","year":"2021","journal-title":"Mol Ther"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800189200","article-title":"Interferon-gamma reduces cell surface expression of annexin 2 and suppresses the invasive capacity of prostate cancer cells","volume":"283","author":"Hastie","year":"2008","journal-title":"J Biol Chem"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2021.1962591","article-title":"IFN-\u03b3-induced ER stress impairs autophagy and triggers apoptosis in lung cancer cells","volume":"10","author":"Fang","year":"2021","journal-title":"Oncoimmunology"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00980-14","article-title":"PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum stress-induced inflammation","volume":"34","author":"Meares","year":"2014","journal-title":"Mol Cell Biol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1038\/sj.embor.7400891","article-title":"Interferons induce tyrosine phosphorylation of the eIF2alpha kinase PKR through activation of Jak1 and Tyk2","volume":"8","author":"Su","year":"2007","journal-title":"EMBO Rep"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.738021","article-title":"Attenuation of PKR-like ER kinase (PERK) signaling selectively controls endoplasmic reticulum stress-induced inflammation without compromising immunological responses","volume":"291","author":"Guthrie","year":"2016","journal-title":"J Biol Chem"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"B87","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nature11247","article-title":"An integrated encyclopedia of DNA elements in the human genome","volume":"489","year":"2012","journal-title":"Nature"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq466","article-title":"ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments","volume":"26","author":"Lachmann","year":"2010","journal-title":"Bioinformatics"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004","article-title":"Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities","volume":"38","author":"Heinz","year":"2010","journal-title":"Mol Cell"},{"key":"B90","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/s41392-024-01980-4","article-title":"The multiple roles of interferon regulatory factor family in health and disease","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.18.8104-8112.2004","article-title":"Global role of TATA box-binding protein recruitment to promoters in mediating gene expression profiles","volume":"24","author":"Kim","year":"2004","journal-title":"Mol Cell Biol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2023.148027","article-title":"The kruppel-like factor (KLF) family, diseases, and physiological events","volume":"895","author":"Yuce","year":"2024","journal-title":"Gene"},{"key":"B93","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41392-023-01732-w","article-title":"TEA domain transcription factor 1(TEAD1) induces cardiac fibroblasts cells remodeling through BRD4\/Wnt4 pathway","volume":"9","author":"Song","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1038\/nature20603","article-title":"Epigenetic stress responses induce muscle stem-cell ageing by Hoxa9 developmental signals","volume":"540","author":"Schw\u00f6rer","year":"2016","journal-title":"Nature"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12320","article-title":"CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity","volume":"7","author":"Jacoby","year":"2016","journal-title":"Nat Commun"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0000000000000169","article-title":"CD19 isoforms enabling resistance to CART-19 immunotherapy are expressed in B-ALL patients at initial diagnosis","volume":"40","author":"Fischer","year":"2017","journal-title":"J Immunother"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.02.068","article-title":"4-Phenylbutyric acid regulates CCl4-induced acute hepatic dyslipidemia in a mouse model: A mechanism-based PK\/PD study","volume":"777","author":"Lee","year":"2016","journal-title":"Eur J Pharmacol"},{"key":"B98","doi-asserted-by":"publisher","first-page":"33","DOI":"10.12688\/f1000research.29032.3","article-title":"Sustainable data analysis with Snakemake","volume":"10","author":"M\u00f6lder","year":"2021","journal-title":"F1000Res"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"B100","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinf"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1101\/060012","article-title":"Fast gene set enrichment analysis","author":"Korotkevich","year":"2021","journal-title":"bioRxiv"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1772472\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:13:46Z","timestamp":1773756826000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1772472\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":105,"alternative-id":["10.3389\/fimmu.2026.1772472"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1772472","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]},"article-number":"1772472"}}