RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:GAS-STING: a classical DNA recognition pathways to tumor therapy.
GAS-STING: a classical DNA recognition pathways to tumor therapy.
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环鸟苷酸-腺苷酸合成酶(cGAS)被认为是细胞内主要的DNA感受器,能够识别外源DNA分子以及游离DNA片段。这一识别过程通过干扰素基因激活因子(STING)促进I型IFN的产生,进而诱导下游转录因子的磷酸化。这一作用体现了cGAS-STING通路最典型的生物学功能。当细胞接受抗肿瘤药物治疗时,DNA损伤会触发cGAS-STING通路的激活,最终导致I型IFN及相关下游干扰素刺激基因的表达。cGAS-STING是重要的固有免疫通路之一,I型IFN在固有免疫与T细胞抗肿瘤免疫之间的衔接中发挥作用。I型IFN促进炎性细胞(包括NK细胞)在肿瘤部位的募集和激活。I型IFN还能促进树突状细胞(DC)的激活和成熟,改善CD4+ T淋巴细胞的抗原提呈,并增强CD8+ T淋巴细胞的交叉提呈,从而上调抗肿瘤反应。本综述讨论了cGAS-STING信号通路及其在传统肿瘤治疗和免疫治疗中的机制和生物学功能。
Cyclic GMP-AMP synthetase (cGAS), recognized as the primary DNA sensor within cells, possesses the capability to identify foreign DNA molecules along with free DNA fragments. This identification process facilitates the production of type I IFNs through the activator of the interferon gene (STING) which induces the phosphorylation of downstream transcription factors. This action characterizes the most archetypal biological functionality of the cGAS-STING pathway. When treated with anti-tumor agents, cells experience DNA damage that triggers activation of the cGAS-STING pathway, culminating in the expression of type I IFNs and associated downstream interferon-stimulated genes.
cGAS-STING is one of the important innate immune pathways,the role of type I IFNs in the articulation between innate immunity and T-cell antitumour immunity. type I IFNs promote the recruitment and activation of inflammatory cells (including NK cells) at the tumor site.
Type I IFNs also can promote the activation and maturation of dendritic cel(DC), improve the antigen presentation of CD4 + T lymphocytes, and enhance the cross-presentation of CD8 + T lymphocytes to upregulating anti-tumor responses. This review discussed the cGAS-STING signaling and its mechanism and biological function in traditional tumor therapy and immunotherapy.
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