cGAS-STING信号通路在卵巢癌中的研究进展

doi:10.12280/gjfckx.20250696

摘要/Abstract

摘要：

卵巢癌（ovarian cancer，OC）是致死率最高的妇科恶性肿瘤，多数患者确诊时已为晚期，预后不良。环鸟苷酸-腺苷酸合成酶（cyclic GMP-AMP synthase，cGAS）-干扰素基因刺激因子（stimulator of interferon gene，STING）信号通路作为先天免疫的核心枢纽，通过识别胞质异常DNA触发Ⅰ型干扰素应答，在调控抗肿瘤免疫和肿瘤微环境中发挥关键作用。该通路在OC中呈现“双刃剑”特性：急性激活可通过增强树突状细胞抗原提呈、促进CD8+T细胞浸润等机制来强化抗肿瘤免疫；慢性持续激活则通过驱动非经典核因子-κB通路促进肿瘤进展。此外，OC中该通路常因表观遗传沉默或代谢产物抑制等因素失活，进一步削弱免疫监视。基于其双向调控特性，STING激动剂及其与免疫检查点抑制剂、多腺苷二磷酸核糖聚合酶抑制剂、化疗或溶瘤病毒的联合应用，为OC治疗提供了新方向。

关键词: 卵巢肿瘤, 环GMP, 干扰素Ⅰ型, 免疫，先天, 肿瘤逃逸, STING激动剂

Abstract:

Ovarian cancer (OC) is the gynecological malignant tumor with the highest mortality rate. Most patients are diagnosed at an advanced stage and have a poor prognosis. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, as a core hub of innate immunity, triggers type Ⅰ interferon response by recognizing abnormal cytoplasmic DNA and plays a crucial role in regulating anti-tumor immunity and the tumor microenvironment. This pathway shows a "double-edged sword" characteristic in OC. Acute activation can enhance anti-tumor immunity through mechanisms such as enhancing antigen presentation by dendritic cells and promoting CD8+ T cell infiltration. Chronic and persistent activation promotes tumor progression by driving the non-classical nuclear factor-κB pathway. Additionally, this pathway in OC is often inactivated due to factors such as epigenetic silencing or inhibition by metabolites, further weakening immune surveillance. Based on its bidirectional regulatory characteristics, STING agonists and their combined application with immune checkpoint inhibitors, poly (ADP-ribose) polymerase inhibitors, chemotherapy, or oncolytic viruses provide new directions for the treatment of OC.

Key words: Ovarian neoplasms, Cyclic GMP, Interferon type Ⅰ, Immunity, innate, Tumor escape, STING agonist

孙雅歌, 张云凤, 卢悦, 郭京京, 相骁莹, 贾涵, 王悦. cGAS-STING信号通路在卵巢癌中的研究进展[J]. 国际妇产科学杂志, 2025, 52(6): 696-701.

SUN Ya-ge, ZHANG Yun-feng, LU Yue, GUO Jing-jing, XIANG Xiao-ying, JIA Han, WANG Yue. Research Progress on the cGAS-STING Signaling Pathway in Ovarian Cancer[J]. Journal of International Obstetrics and Gynecology, 2025, 52(6): 696-701.

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