{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:56:12Z","timestamp":1792454172009,"version":"4.5.0"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>One-carbon metabolism has emerged as a critical interface between tumor metabolic adaptation and antitumor immunity. Beyond its canonical role in nucleotide biosynthesis and redox balance, this metabolic network regulates methyl-donor availability, epigenetic programming, and immune-cell state transitions within the tumor microenvironment. Recent studies show that tumor cells can outcompete T cells for methionine, thereby depleting intracellular S-adenosylmethionine, impairing histone methylation, and driving effector dysfunction or exhaustion. At the same time, tumor-intrinsic one-carbon enzymes such as MTHFD2 actively promote immune escape through PD-L1 upregulation and suppression of innate immune sensing. Serine-related pathways further shape the immune landscape in a context-dependent manner, supporting either immunosuppressive cell accumulation or enhanced tumor immunogenicity depending on the cellular compartment and metabolic state. Importantly, one-carbon metabolism also represents a therapeutic opportunity. Strategies including methionine restriction, formate supplementation, serine-pathway targeting, and methyl-donor modulation have shown potential to enhance antitumor immunity and improve responses to immune checkpoint blockade. However, because one-carbon metabolism is required by both tumor cells and immune cells, effective intervention will require careful attention to cell-type specificity, metabolic context, and therapeutic timing. In this review, we discuss how one-carbon metabolism governs T-cell fitness, epigenetic regulation, and the broader tumor immune ecosystem, and we highlight emerging translational strategies for exploiting this pathway in cancer immunotherapy.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1867162","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:35:17Z","timestamp":1783920917000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["One-carbon metabolism in cancer immunity: T-cell fitness, epigenetic programming, and therapeutic opportunities"],"prefix":"10.3389","volume":"17","author":[{"given":"Rongfei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Jinhua People\u2019s Hospital","place":["Jinhua, Zhejiang, 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