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However, the mechanisms by which cancer cells influence the differentiation of these cells remain elusive. Herein, we demonstrate that cancer stem cells (CSCs) play a pivotal role in suppressing CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation in patients with non\u2010small cell lung cancer (NSCLC). Specifically, CSCs facilitate the transfer of the metabolite acetyl\u2010coenzyme A (acetyl\u2010CoA) into interacting T cells via an exosome\u2010dependent pathway. This process enhances the acetylation of B lymphocyte\u2010induced maturation protein 1 (Blimp\u20101), a critical transcription factor governing CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation. Acetylation of Blimp\u20101 strengthens its interaction with the E3 ubiquitin ligase LIS1, thereby promoting Blimp\u20101 degradation, which ultimately blocks CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation. Accordingly, targeting CSCs and acetyl\u2010CoA biosynthesis using CD133 antibody\u2010conjugated nanoparticles increases tumor\u2010infiltrating CD8\n                    <jats:sup>+<\/jats:sup>\n                    CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cells and suppresses tumor growth. Importantly, studies using NSCLC patient\u2010derived organoids (PDOs) and humanized PDO\u2010NSG chimeras confirmed that blocking acetyl\u2010CoA production, exosome secretion from CSCs, and key enzymes involved in Blimp\u20101 acetylation and ubiquitination effectively restores CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cell differentiation. Altogether, CSC acetyl\u2010CoA is a key contributor in impairing CD103\n                    <jats:sup>+<\/jats:sup>\n                    T cells through programming post\u2010translational modifications, serving as a promising therapeutic target in anti\u2010tumor therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202513535","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T04:55:56Z","timestamp":1763960156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cancer Stem Cells Shift Metabolite Acetyl\u2010Coenzyme A to Abrogate the Differentiation of CD103\n                    <sup>+<\/sup>\n                    T Cells"],"prefix":"10.1002","volume":"13","author":[{"given":"Jiaxin","family":"Lei","sequence":"first","affiliation":[{"name":"The Fourth Affiliated Hospital of Soochow University Institutes of Biology and Medical Sciences Suzhou Medical College of Soochow 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