2026 年 1 月 5 日， 清华大学基础医学院 傅阳心 教授、 王文彦 助理研究员及 深圳湾实验室肿瘤研究所 卢长征 研究员， 在 Nature 旗下综述期刊 Nature Reviews Cancer 上发表了题为： Opportunities and challenges of targeting cGAS–STING in cancer 的综述论文。 该综述论文系统阐述了关于 cGAS-STING 通路介导的 促癌与抑癌双重作用 的重要研究进展，并深入探讨了其融入未来癌症免疫治疗的机遇与挑战。 编辑丨王多鱼 排版丨水成文 环鸟苷酸-腺苷酸合成酶 （cGAS） -干扰素基因刺激因子 （STING） 通路在检测肿瘤源性 DNA 方面发挥关键作用，无论是自发产生还是治疗诱导产生的该通路 皆然。cGAS-STING 通路的激活，会触发肿瘤细胞和免疫细胞中的 I 型干扰素信号转导及促炎反应，从而在病理性炎症与保护性免疫应答之间建立微妙平衡。 尽管临床前研究揭示了靶向 cGAS-STING 通路以增强抗肿瘤免疫疗法的潜力，但临床实验结果却未达预期。 该综述的特色之一，全面分析了 cGAS–STING 通路的激活 ...

Core Viewpoint - Colorectal cancer (CRC) is the third leading cause of cancer-related deaths globally, with over 30% of patients diagnosed at an advanced stage. Neoadjuvant radiotherapy plays a crucial role in both curative and palliative treatments, yet only 15%-30% of rectal cancer patients achieve pathological complete response (pCR), highlighting the need to understand mechanisms behind radiotherapy failure [2][5]. Group 1 - A new study published in Cell Reports Medicine identifies a subtype of cancer-associated fibroblasts (CAFs) called ilCAF, which responds positively to radiotherapy. Activation of the IFN-γ/STING signaling pathway in ilCAF enhances the effectiveness of radiotherapy and overcomes resistance [3][6]. - The study utilized single-cell RNA sequencing to discover ilCAF characterized by high expression of interferon regulatory factor-1 (IRF1), which is enriched in tumors that respond well to radiotherapy [6][9]. - The activation of the IFN-γ/STING signaling pathway reprograms the tumor microenvironment, enhancing anti-tumor immunity by attracting T cells and dendritic cells through the secretion of chemokines CCL4 and CCL5 [6][12]. Group 2 - The increase in ilCAF numbers enhances endogenous immune responses, contributing to improved overall survival rates in rectal cancer patients. The combination of STING agonists with radiotherapy shows significant translational potential for cancer treatment [9][12]. - Early initiation of the combined strategy of STING agonists and radiotherapy may enhance initial anti-tumor responses and mitigate the emergence of treatment resistance [9].