Lipid metabolism: a potential checkpoint for cGAS-STING regulation in colorectal cancer
4 affiliations
- 1Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- 2Hubei Provincial Clinical Research Center for Minimally Invasive Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- 3Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- 4Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Abstract
Immunotherapy for colorectal cancer (CRC) continues to face significant challenges, particularly in patients with microsatellite stable (MSS) tumors. The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) 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–STING 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–STING signaling in tumor immunity. We further examine potential mechanisms by which lipid metabolism may influence cGAS–STING 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–STING 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–STING signaling to balance intestinal inflammation and anti-tumor immunity. Finally, we discuss therapeutic strategies targeting lipid metabolism and cGAS–STING 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.
Related
- Immune checkpoint inhibitors combined with VEGF/VEGFR-targeted therapy in microsatellite-stable advanced colorectal cancer: clinical advances and the potential for immune-sensitive tumor conversion
- Site-specific immune remodeling underlies resistance to dual immune checkpoint blockade in metastatic colorectal cancer
- Integrated Transcriptomic Analysis Identifies ENO3 as a Candidate Lactate Metabolism‐Associated Biomarker in Colorectal Cancer Metastasis
- Chitosan nanoparticles functionalised with protocatechuic acid improve colon-targeted pazopanib delivery with multi-pathway therapeutic regulation and pharmacokinetic optimisation in colorectal cancer
- TRPML1 inhibitor ML-SI1 suppresses prostate cancer through dual regulation of androgen receptor and polyamine metabolism
BibTeX
@article{qiu2026lipid,
title = {{Lipid metabolism: a potential checkpoint for cGAS-STING regulation in colorectal cancer}},
author = {Qi Qiu and Zhihong Cheng and Jian Gu and Tao Zhang and Mingdong Cai and Jiliang Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1928380},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1928380/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lipid metabolism: a potential checkpoint for cGAS-STING regulation in colorectal cancer
AU - Qi Qiu
AU - Zhihong Cheng
AU - Jian Gu
AU - Tao Zhang
AU - Mingdong Cai
AU - Jiliang Wang
PY - 2026
DA - 2026/10/05
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1928380
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1928380/full
AB - Immunotherapy for colorectal cancer (CRC) continues to face significant challenges, particularly in patients with microsatellite stable (MSS) tumors. The cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) 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–STING 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–STING signaling in tumor immunity. We further examine potential mechanisms by which lipid metabolism may influence cGAS–STING 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–STING 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–STING signaling to balance intestinal inflammation and anti-tumor immunity. Finally, we discuss therapeutic strategies targeting lipid metabolism and cGAS–STING 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.
SN - 1664-3224
ER -