{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:53:19Z","timestamp":1790931199664,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007428","name":"Naito Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006680","name":"Takeda Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006680","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K27427"],"award-info":[{"award-number":["23K27427"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K11367"],"award-info":[{"award-number":["24K11367"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K18470"],"award-info":[{"award-number":["24K18470"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K10214"],"award-info":[{"award-number":["25K10214"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Appropriate regulation of the differentiation balance between effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells is crucial for an appropriate immune response. We previously reported that the tumor suppressor menin suppresses the differentiation of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells into short\u2010lived effector T cells (SLECs) and positively regulates memory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation. In this study, we identified Ezh2, a histone H3K27 methyltransferase, as a factor responsible for regulating SLECs differentiation, located downstream of menin. In antigen\u2010stimulated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, the Ezh2 expression gradually decreased with proliferation, reaching the lowest levels in terminally differentiated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. The decrease in the expression of Ezh2 was accelerated by menin deficiency. Reduced histone H3K27 acetylation at the\n                    <jats:italic>Ezh2<\/jats:italic>\n                    locus was observed in\n                    <jats:italic>Menin<\/jats:italic>\n                    \u2010deficient CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, indicating that menin is required for maintaining the expression of Ezh2. In\u00a0vitro studies have demonstrated that\n                    <jats:italic>Ezh2<\/jats:italic>\n                    \u2010deficient activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells exhibit enhanced differentiation into SLECs, along with increased effector functions. In contrast, Ezh2\u2010deficient effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells showed a marked increase in apoptosis upon IL\u20102 removal. In studies using mouse tumor models, T cell\u2010specific Ezh2 knockout mice exhibited increased tumor growth and reduced survival relative to wild\u2010type mice, with a significant decrease in the number of tumor\u2010infiltrating CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. RNA sequencing revealed that\n                    <jats:italic>Ezh2<\/jats:italic>\n                    \u2010deficient effector CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells exhibit the increased expression of terminal differentiation\u2010related molecules and apoptosis\u2010related genes. These results demonstrate that Ezh2 functions downstream of menin and is essential for the proper regulation of T cell\u2010dependent antitumor immunity.\n                  <\/jats:p>","DOI":"10.1111\/cas.70439","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:40:46Z","timestamp":1780400446000},"page":"2644-2658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ezh2 Inhibits the Differentiation of Short\u2010Lived Effector\n                    <scp>CD8<\/scp>\n                    <sup>+<\/sup>\n                    T Cells and Promotes T Cell\u2010Dependent Antitumor Immunity"],"prefix":"10.1111","volume":"117","author":[{"given":"Kenji","family":"Takagi","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery and Surgical Oncology Ehime University Graduate School of Medicine  Toon Ehime Japan"},{"name":"Department of Immunology Ehime University, Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpei","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Immunology Ehime University, Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Translational Research Center, Ehime University Hospital Ehime University  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Kuwahara","sequence":"additional","affiliation":[{"name":"Department of Immunology Ehime University, Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Oshikiri","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery and Surgical Oncology Ehime University Graduate School of Medicine  Toon Ehime Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8975-3513","authenticated-orcid":false,"given":"Masakatsu","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Department of Immunology Ehime University, Graduate School of Medicine  Toon Ehime Japan"},{"name":"Translational Research Center, Ehime University Hospital Ehime University  Toon Ehime Japan"},{"name":"Department of Infections and Host Defenses Ehime University, Graduate School of Medicine  Toon Ehime 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