{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:54:07Z","timestamp":1791179647606,"version":"4.1.0"},"reference-count":211,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"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>Immunotherapy for colorectal cancer (CRC) continues to face significant challenges, particularly in patients with microsatellite stable (MSS) tumors. The cyclic GMP\u2013AMP synthase\u2013stimulator of interferon genes (cGAS\u2013STING) pathway is a key regulator of innate immunity and has emerged as a promising target for enhancing anti-tumor immune responses. Meanwhile, lipid metabolic reprogramming is a defining hallmark of CRC and contributes to tumor progression, evasion, and therapeutic resistance. Although direct evidence linking lipid metabolism to cGAS\u2013STING signaling in CRC remains limited, accumulating studies from diverse disease models suggest extensive interactions between these two processes. This review summarizes the major features of lipid metabolic reprogramming in CRC and discusses current understanding of cGAS\u2013STING signaling in tumor immunity. We further examine potential mechanisms by which lipid metabolism may influence cGAS\u2013STING activity, including the regulation of mitochondrial DNA release, intracellular trafficking of signaling components and lipid-associated post-translational modifications. Emerging evidence also indicates that cGAS\u2013STING signaling can affect lipid metabolic pathways by regulating lipid metabolic homeostasis and inducing lipid peroxidation-driven ferroptosis. Importantly, microbiota-derived lipid metabolites exert context-dependent effects on cGAS\u2013STING signaling to balance intestinal inflammation and anti-tumor immunity. Finally, we discuss therapeutic strategies targeting lipid metabolism and cGAS\u2013STING signaling, with a particular focus on approaches that may enhance anti-tumor immunity through coordinated metabolic-immune modulation. By bridging metabolic reprogramming with innate immune sensing, we propose that modulating the lipid-cGAS-STING axis could break immune tolerance and offer a distinct therapeutic window for CRC.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1928380","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:32:43Z","timestamp":1791178363000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid metabolism: a potential checkpoint for cGAS-STING regulation in colorectal cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Qi","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Hubei Provincial Clinical Research Center for Minimally Invasive Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science 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