{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:55:42Z","timestamp":1790920542981,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA193939, P30CA016058, CA163910"],"award-info":[{"award-number":["CA193939, P30CA016058, CA163910"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells play a crucial role in anti-tumor immunity; however, their functionality is compromised by exhaustion driven by chronic antigen exposure, poor tumor microenvironment, and metabolic dysfunction. Activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells undergo extensive proteomic remodeling, which includes the induction of the IRE1-XBP1 signaling axis of the unfolded protein response. However, the functional consequences of sustained IRE1-XBP1 activation in exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells remain elusive. Using a model of constitutive XBP1 activation in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, we demonstrate that sustained XBP1s signaling leads to reduced homeostatic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell populations, impaired migratory capacity, and dampened anti-tumor immunity. Notably, pharmacological inhibition of the IRE1-XBP1 axis significantly reduces tumor burden through a dual mechanism that targets both tumor cells and the immune compartment. Our findings reveal a previously unappreciated role for XBP1s in regulating CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell biology and highlight the IRE1-XBP1 axis as a therapeutic target in solid tumors.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1940201","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:37:34Z","timestamp":1790919454000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic XBP1s-mediated activation of the unfolded protein response impairs CD8+ T cell anti-tumor immunity"],"prefix":"10.3389","volume":"17","author":[{"suffix":"II","given":"Keith Alan","family":"Nair","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center","place":["Columbus, OH, United States"]},{"name":"The Pelotonia Institute for Immuno-Oncology, 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Andrew","family":"Hu","sequence":"additional","affiliation":[{"name":"Houston Methodist Neal Cancer Center, Houston Methodist Research Institute","place":["Houston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley Ching-Cheng","family":"Huang","sequence":"additional","affiliation":[{"name":"The Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center","place":["Columbus, OH, United States"]},{"name":"Department of Microbial Infection and Immunity, The Ohio State University College of Medicine","place":["Columbus, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wieland","sequence":"additional","affiliation":[{"name":"The Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center","place":["Columbus, OH, United States"]},{"name":"Department of Otolaryngology-Head and Neck Surgery, The Ohio State University College of Medicine","place":["Columbus, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem E.","family":"Ghoneim","sequence":"additional","affiliation":[{"name":"The Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center","place":["Columbus, OH, United States"]},{"name":"Department of Microbial Infection and Immunity, The Ohio State University College of Medicine","place":["Columbus, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haitao","family":"Wen","sequence":"additional","affiliation":[{"name":"The Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center","place":["Columbus, OH, United States"]},{"name":"Department of Microbial Infection and Immunity, The Ohio State University College of Medicine","place":["Columbus, OH, United 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