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However, the mechanism of Acetyl coenzyme A availability in pancreatic neuroendocrine tumors (PNETs) remains largely unknown. Herein, the metabolic\u2010epigenetic modification driven by acetyl coenzyme A synthase 2 (ACSS2) and its effect on the Fas\/FasL system in PNETs is investigated. ACSS2 is highly expressed in PNETs and significantly correlated with patient prognosis. Mechanistically, ACSS2 activity or acetate supplementation induces histone H3\/H4 hyperacetylated in PNET cells. This epigenetic modification recruits the transcription factor AATF to co\u2010regulate FasL transcription, specifically enhancing soluble FasL secretion. Secreted FasL binds Fas receptors on CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, activating caspase\u20108\/3 cascades to trigger T\u2010cell apoptosis and promote immune evasion. Notably, the finding indicated the non\u2010redundant and synergistic effects of ACSS2 and AATF in modulating FasL expression, which might support emerging strategies for immunotherapy of PNETs.\n                  <\/jats:p>","DOI":"10.1002\/advs.202506883","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T08:48:58Z","timestamp":1754988538000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ACSS2\/AATF Drives Soluble FasL\u2010Mediated CD8\n                    <sup>+<\/sup>\n                    T Cell Apoptosis in Pancreatic Neuroendocrine Tumors"],"prefix":"10.1002","volume":"12","author":[{"given":"Qin","family":"Dang","sequence":"first","affiliation":[{"name":"Department of Pancreatic Surgery Fudan University Shanghai Cancer Center  Shanghai 200032 China"},{"name":"Department of Oncology Shanghai Medical College Fudan University  Shanghai 200032 China"},{"name":"Shanghai 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