Immunotherapy Inhibits Tumor Cholesterol Synthesis via the IFNγ–IRF1–SREBF2 Axis

作者：Liping Xu, Xiaomin Zhang, Xiaowei Lai, Hongyuan Chen, Shuangye Liao, M L Chang, Xiaoqing Wu, Wen Rui, Juan Yang, Danyang Wang, Changjun Gao, Ziqian Fang, Jianeng Zhang, Wende Li, Bo Li, Xiaojun Xia, Penghui Zhou · 发表于：Cancer Immunology Research · 年份：2025 · DOI：10.1158/2326-6066.cir-25-0242 · 被引用次数：1 · 研究领域：Cancer, Lipids, and Metabolism、Cholesterol and Lipid Metabolism、Cancer Immunotherapy and Biomarkers

Tumor cells employ metabolic mechanisms to limit antitumor immunity and promote resistance to immunotherapy. However, how immunotherapy modulates tumor metabolism remains unclear. In this study, we demonstrated that anti-PD-1 treatment regulated cholesterol biosynthesis in cancer cells through the effector cytokine IFNγ. Mechanistically, IFNγ-induced IRF1 transcriptionally suppresses the expression of SREBF2, a master regulator of cholesterol synthesis. Reduced cholesterol content inhibited tumor growth and sensitized tumor cells to statins, drugs that can lower cholesterol. Overall, our study reveals that IFNγ-mediated inhibition of cholesterol biosynthesis in tumor cells is an important antitumor mechanism of immunotherapy.