{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:16:56Z","timestamp":1791433016488,"version":"4.3.3"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100017292","name":"Ovarian Cancer Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP\u2010142351"],"award-info":[{"award-number":["MOP\u2010142351"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010162279"],"award-info":[{"award-number":["PJT\u2010162279"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102022\u201003696"],"award-info":[{"award-number":["RGPIN\u20102022\u201003696"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102017\u201004162"],"award-info":[{"award-number":["RGPIN\u20102017\u201004162"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R35CA220449"],"award-info":[{"award-number":["R35CA220449"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP240494"],"award-info":[{"award-number":["RP240494"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Methionine is an essential amino acid critical for T cell activation. While methionine restriction (MR) combined with immune checkpoint blockade has been shown to enhance T cell function, the impact of methionine on adoptive T cell therapies remains unknown. Here, we examined the functionality of T cells under MR and pharmaceutical inhibition of the methionine cycle (MAT2Ai), using primary T cells and a murine adoptive T cell therapy model. In\u00a0vitro, transient MR or MAT2Ai treatment increased interferon gamma (IFN\u03b3) expression in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, whereas sustained MR led to the upregulation of T cell exhaustion\u2010associated markers. Mechanistically, transient MR suppressed the polyamine synthesis pathway, and supplementation with polyamines reversed MR\u2010induced IFN\u03b3 expression. Genetic ablation of S\u2010adenosylmethionine decarboxylase, an enzyme involved in the polyamine synthesis pathway, recapitulated the effect of MR, indicating that transient MR enhances T cell function by inhibiting polyamine synthesis. Despite this, transient MR treatment of ovalbumin (OVA)\u2010specific (OT\u2010I) CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells prior to adoptive transfer did not improve antitumour efficacy against EG7\u2010OVA tumours in\u00a0vivo. In contrast, sustained dietary MR accelerated EG7\u2010OVA tumour growth in mice treated with OT\u2010I T cells, demonstrating that methionine availability is essential for the activity of donor T cells. Importantly, sustained dietary MR promoted terminally exhausted phenotype in tumour\u2010infiltrating donor CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, but not in host T cells. These findings suggest that enhancing methionine availability in the tumour microenvironment may improve the efficacy of adoptive T cell therapies.\n                  <\/jats:p>","DOI":"10.1111\/imm.70177","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T02:11:39Z","timestamp":1785118299000},"page":"418-433","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Methionine Regulates Antitumour Function of\n                    <scp>CD8<\/scp>\n                    <sup>+<\/sup>\n                    T Cells Through Polyamine Synthesis"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5715-1884","authenticated-orcid":false,"given":"Tian","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Molecular Life Sciences University of Victoria  Victoria British Columbia Canada"},{"name":"Trev and Joyce Deeley Research Centre BC Cancer  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian A.","family":"Carleton","sequence":"additional","affiliation":[{"name":"School of Molecular Life Sciences University of Victoria  Victoria British Columbia Canada"},{"name":"Trev and Joyce Deeley Research Centre BC Cancer  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Preshaw","sequence":"additional","affiliation":[{"name":"School of Molecular Life Sciences University of Victoria  Victoria British Columbia Canada"},{"name":"Trev and Joyce Deeley Research Centre BC Cancer  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"MacPherson","sequence":"additional","affiliation":[{"name":"Trev and Joyce Deeley Research Centre BC Cancer  Victoria British Columbia Canada"},{"name":"Basic and Translational Research BC Cancer Research Institute, BC Cancer  Victoria British 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Victoria  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oro","family":"Uchenunu","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Rottapel","sequence":"additional","affiliation":[{"name":"Princess Margaret Cancer Centre, University Health Network University of Toronto  Toronto Ontario Canada"},{"name":"Department of Medical Biophysics University of Toronto  Toronto Ontario Canada"},{"name":"Ontario Institute for Cancer Research  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph J.","family":"DeBerardinis","sequence":"additional","affiliation":[{"name":"Children's Medical Center Research Institute University of Texas Southwestern Medical Center  Dallas Texas USA"},{"name":"Eugene McDermott Center for Human Growth and Development University of Texas Southwestern Medical Center  Dallas Texas USA"},{"name":"Howard Hughes Medical Institute University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Agios Pharmaceuticals  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2595-4890","authenticated-orcid":false,"given":"Bo\u2010Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Molecular Life Sciences University of Victoria  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Ausi\u00f3","sequence":"additional","affiliation":[{"name":"School of Molecular Life Sciences University of Victoria  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Goodlett","sequence":"additional","affiliation":[{"name":"School of Molecular Life Sciences University of Victoria  Victoria British Columbia Canada"},{"name":"University of Victoria Genome BC Proteomics Centre University of Victoria  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9756-7236","authenticated-orcid":false,"given":"Helena","family":"P\u011btro\u0161ov\u00e1","sequence":"additional","affiliation":[{"name":"School of Molecular Life Sciences University of Victoria  Victoria British Columbia Canada"},{"name":"University of Victoria Genome BC Proteomics Centre University of Victoria  Victoria British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0575-0858","authenticated-orcid":false,"given":"Kyle 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