The cGAS/STING pathway is a crucial immune activator in cancer biology, triggering innate immunosurveillance against tumors by sensing and reacting to endogenous mitochondrial DNA (mtDNA). In this issue of Cancer Research, research by Saha and colleagues highlights the significant impact of serine deprivation on this pathway, thereby unveiling its potential for anticancer therapy. Serine is essential for cellular metabolism and influences tumor growth and immune responses. Depriving cells of serine caused mitochondrial dysfunction and the release of mtDNA into the cytosol, activating the cGAS/STING pathway and inducing type I IFN responses. In mouse models, serine deprivation enhanced antitumor immunity, with increased tumoral immune infiltration, including CD4+/CD8+ T cells and type I IFN responses. Clinically, a genetic signature indicative of lower serine enrichment in colorectal cancer patients correlated with immune activation and improved survival. Furthermore, combining serine deprivation with PD1 blockade significantly reduced tumor volume and led to long-term immunity in mice, suggesting that serine depletion enhances the efficacy of immune checkpoint blockade. These findings propose serine deprivation as a promising strategy to boost antitumor immunity and improve cancer patient outcomes. See related article by Saha et al., p. 2645

中文翻译：

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激活 cGAS/STING 驱动抗癌免疫的免疫代谢途径


cGAS/STING 通路是癌症生物学中重要的免疫激活剂，通过感知内源性线粒体 DNA (mtDNA) 并对其做出反应，触发针对肿瘤的先天免疫监视。在本期《癌症研究》中，Saha 及其同事的研究强调了丝氨酸剥夺对该途径的重大影响，从而揭示了其抗癌治疗的潜力。丝氨酸对于细胞代谢至关重要，并影响肿瘤生长和免疫反应。剥夺细胞丝氨酸会导致线粒体功能障碍和 mtDNA 释放到细胞质中，激活 cGAS/STING 途径并诱导 I 型 IFN 反应。在小鼠模型中，丝氨酸剥夺增强了抗肿瘤免疫力，增加了肿瘤免疫浸润，包括 CD4+/CD8+ T 细胞和 I 型 IFN 反应。临床上，表明结直肠癌患者丝氨酸富集较低的遗传特征与免疫激活和生存改善相关。此外，将丝氨酸剥夺与PD1阻断相结合可显着缩小肿瘤体积，并导致小鼠产生长期免疫力，这表明丝氨酸缺失增强了免疫检查点阻断的功效。这些发现表明丝氨酸剥夺是增强抗肿瘤免疫力和改善癌症患者预后的一种有前景的策略。参见 Saha 等人的相关文章，第 17 页。 2645