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To investigate T cell states associated with reduced ICI efficacy, we performed single\u2010cell RNA sequencing (scRNA\u2010seq) on tumor\u2010infiltrating lymphocytes (TILs) from a patient experiencing rapid recurrence under PD\u20101 blockade. Our analysis identified elevated expression of the\n                    <jats:italic>ZFP36<\/jats:italic>\n                    family of RNA\u2010binding proteins within exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells (T\n                    <jats:sub>ex<\/jats:sub>\n                    cells) in this progressing tumor. The ZFP36 family is known to destabilize target mRNAs by binding to AU\u2010rich elements in their 3\u2032 untranslated regions (3\u2032 UTRs). In EL4 T cells,\n                    <jats:italic>Zfp36<\/jats:italic>\n                    overexpression accelerated the decay of the effector cytokine mRNAs\n                    <jats:italic>Tnf<\/jats:italic>\n                    ,\n                    <jats:italic>Il2<\/jats:italic>\n                    , and\n                    <jats:italic>Ifng<\/jats:italic>\n                    , thereby impairing cytokine production. This process is exacerbated by hypoxia. Furthermore, high\n                    <jats:italic>ZFP36<\/jats:italic>\n                    family expression correlates with poor prognosis in ICI\u2010treated patients in a public bulk tumor transcriptomic dataset. These findings suggest that tumor microenvironment (TME)\u2010induced hypoxia upregulates the\n                    <jats:italic>ZFP36<\/jats:italic>\n                    family in T\n                    <jats:sub>ex<\/jats:sub>\n                    cells, which in turn suppresses cytokine production via post\u2010transcriptional regulation, potentially contributing to impaired antitumor effector function.\n                  <\/jats:p>","DOI":"10.1111\/cas.70546","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:48:22Z","timestamp":1790678902000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High\n                    <scp>ZFP36<\/scp>\n                    Family Expression in Exhausted T Cells Is Associated With Impaired Antitumor Effector Function"],"prefix":"10.1111","author":[{"given":"Li","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2627-8524","authenticated-orcid":false,"given":"Youki","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Inutsuka","sequence":"additional","affiliation":[{"name":"Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama University  Okayama Japan"},{"name":"Department of Respiratory Medicine, Graduate School of Medical Sciences Kyushu University  Fukuoka 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