{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:00:54Z","timestamp":1784696454475,"version":"3.55.0"},"reference-count":5,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      In a recent study published in\n                      <jats:italic toggle=\"yes\">Science Immunology<\/jats:italic>\n                      , Tiberti and colleagues demonstrate that palmitate, a saturated fatty acid enriched in tumors, directly impairs CD8\n                      <jats:sup>+<\/jats:sup>\n                      cytotoxic T lymphocyte function through mitochondrial and epigenetic reprogramming. Palmitate exposure reduced mitochondrial fitness, oxidative phosphorylation, and adenosine triphosphate production, resulting in defective proliferation, cytokine production, and antitumor activity. Mechanistically, mitochondrial dysfunction decreased intracellular acetyl-CoA availability, leading to reduced histone acetylation and loss of chromatin accessibility at loci that control effector programs. The study further identifies sphingosine kinase 2 as a critical mediator of lipid-induced dysfunction. Importantly, SPHK2 inhibition restored mitochondrial function, histone acetylation, and cytotoxic T lymphocyte antitumor activity, highlighting a potential therapeutic strategy for enhancing cancer immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/in9.0000000000000086","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:02:13Z","timestamp":1784692933000},"page":"e00086","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Lipid-driven epigenetic exhaustion: linking palmitate metabolism to CD8+ T-cell dysfunction in cancer"],"prefix":"10.1097","volume":"8","author":[{"given":"Desh","family":"Raj","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA"},{"name":"Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Kathania","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA"},{"name":"Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuoqi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianne L.","family":"Theiss","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Venuprasad","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA"},{"name":"Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA"},{"name":"Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7]]},"reference":[{"issue":"1","key":"R1-20260722","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s43018-023-00702-z","article-title":"Lipids as mediators of cancer progression and metastasis.","volume":"5","author":"Vogel","year":"2024","journal-title":"Nat Cancer"},{"issue":"117","key":"R2-20260722","doi-asserted-by":"crossref","first-page":"eaeb1459","DOI":"10.1126\/sciimmunol.aeb1459","article-title":"Palmitate-induced mitochondrial damage restricts histone acetylation in CD8 T cells to impair antitumor immunity.","volume":"11","author":"Tiberti","year":"2026","journal-title":"Sci Immunol"},{"issue":"4","key":"R3-20260722","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.immuni.2013.04.005","article-title":"Metabolic pathways in immune cell activation and quiescence.","volume":"38","author":"Pearce","year":"2013","journal-title":"Immunity"},{"issue":"6","key":"R4-20260722","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.cell.2015.08.012","article-title":"Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses.","volume":"162","author":"Ho","year":"2015","journal-title":"Cell"},{"issue":"8","key":"R5-20260722","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion.","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat Rev Immunol"}],"container-title":["Immunometabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/IN9.0000000000000086","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:02:13Z","timestamp":1784692933000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/IN9.0000000000000086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":5,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1097\/in9.0000000000000086","relation":{},"ISSN":["2633-0407"],"issn-type":[{"value":"2633-0407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-05-22","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-29","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}