{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:56:25Z","timestamp":1791197785086,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010481","name":"Etablissement Fran\u00e7ais du Sang","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010481","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014808","name":"Groupement des Entreprises Fran\u00e7aises dans la lutte contre le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014808","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR\u201011\u2010LABX\u20100021"],"award-info":[{"award-number":["ANR\u201011\u2010LABX\u20100021"]}],"id":[{"id":"10.13039\/501100001665","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                    Metabolism is critical for immune cell functions. Tumours shape their microenvironment to render it metabolically hostile for infiltrating immune cells. While targeting immunometabolism emerges as a promising way to reinvigorate anticancer immunity, a deeper understanding of the metabolic disturbances of immune cells is needed. Here, we explored how the metabolic status of T cells governs immune skewing from circulating and tumour\u2010infiltrating CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells of melanoma patients at a single\u2010cell level using the SCENITH method and targeted metabolomics. Circulating and tumour\u2010infiltrating T cells from patients displayed a decreased mitochondrial dependency associated with an enhanced glycolytic capacity and a skewed metabolic reprogramming upon stimulation. Such metabolic disturbances were linked to the activation status, immune checkpoint profile and functional orientation of T cells, underlining critical connections between T\u2010cell features and metabolic patterns. Targeted metabolomics within sorted CD4\n                    <jats:sup>+<\/jats:sup>\n                    \/CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells identified a decrease in citrulline, cysteine and threonine within all subsets in patients, together with a sharp rise in sterol cholesterol CE(20:2) and ceramide dhCer(d18:0\/22:0) within tumour\u2010infiltrating CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and in glycerolipid DG(16:0\/16:0) within CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in blood and tumour. We further outlined a metabolic\u2010checkpoint\u2010based signature composed of six genes coding enzymes\/transporters connected to the imbalanced metabolites found within tumour\u2010infiltrating T cells (\n                    <jats:italic>LIPA<\/jats:italic>\n                    ,\n                    <jats:italic>DGKA<\/jats:italic>\n                    ,\n                    <jats:italic>GLUL<\/jats:italic>\n                    ,\n                    <jats:italic>SLC38A1<\/jats:italic>\n                    ,\n                    <jats:italic>SLC7A7<\/jats:italic>\n                    ,\n                    <jats:italic>GCH1<\/jats:italic>\n                    ) that shape patients' clinical outcome. These findings outline the skewed bioenergetic profiles of T cells and depict metabolic checkpoints associated with immune subversion. Harnessing metabolic pathways is promising for developing innovative therapies to restore optimal anti\u2010tumour responses and improve clinical success.\n                  <\/jats:p>","DOI":"10.1111\/imm.70185","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:16:18Z","timestamp":1785903378000},"page":"486-515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Profiling of Circulating and Tumour\u2010Infiltrating T Cells Uncovers Bioenergetic Checkpoints Linked With Immune and Clinical Skewing in Melanoma Patients"],"prefix":"10.1111","volume":"179","author":[{"given":"Hugo","family":"Brouque","sequence":"first","affiliation":[{"name":"Institute for Advanced Biosciences, Team: Immunology &amp; Immunotherapy of Chronic Diseases, Inserm U 1209, CNRS UMR 5309 Univ. Grenoble Alpes  Grenoble France"},{"name":"Etablissement Fran\u00e7ais du Sang Auvergne\u2010Rh\u00f4ne\u2010Alpes, R&amp;D Laboratory  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kareem","family":"Mahdy","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, Team: Immunology &amp; Immunotherapy of Chronic Diseases, Inserm U 1209, CNRS UMR 5309 Univ. Grenoble Alpes  Grenoble France"},{"name":"Etablissement Fran\u00e7ais du Sang Auvergne\u2010Rh\u00f4ne\u2010Alpes, R&amp;D Laboratory  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3880-973X","authenticated-orcid":false,"given":"Stephane","family":"Mouret","sequence":"additional","affiliation":[{"name":"Dermatology, Allergology &amp; Photobiology Department, CHU Grenoble Alpes Univ. Grenoble Alpes  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3460-8324","authenticated-orcid":false,"given":"Sylvain","family":"Henry","sequence":"additional","affiliation":[{"name":"Platform for Translational Oncometabolomics, Biocampus, CNRS, INSERM Universit\u00e9 de Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Niveau","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, Team: Immunology &amp; Immunotherapy of Chronic Diseases, Inserm U 1209, CNRS UMR 5309 Univ. Grenoble Alpes  Grenoble France"},{"name":"Etablissement Fran\u00e7ais du Sang Auvergne\u2010Rh\u00f4ne\u2010Alpes, R&amp;D Laboratory  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Cettour\u2010Cave","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biosciences, Team: Immunology &amp; Immunotherapy of Chronic Diseases, Inserm U 1209, CNRS UMR 5309 Univ. 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