Jiang Minlin, Jia Keyi, Wang Lei, Li Wei, Chen Bin, Liu Yu, Wang Hao, Zhao Sha, He Yayi, Zhou Caicun
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.
Medical School, Tongji University, Shanghai 200433, China.
Acta Pharm Sin B. 2021 Oct;11(10):2983-2994. doi: 10.1016/j.apsb.2021.01.003. Epub 2021 Jan 6.
Genomic instability remains an enabling feature of cancer and promotes malignant transformation. Alterations of DNA damage response (DDR) pathways allow genomic instability, generate neoantigens, upregulate the expression of programmed death ligand 1 (PD-L1) and interact with signaling such as cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling. Here, we review the basic knowledge of DDR pathways, mechanisms of genomic instability induced by DDR alterations, impacts of DDR alterations on immune system, and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy.
基因组不稳定仍然是癌症的一个促成特征,并促进恶性转化。DNA损伤反应(DDR)途径的改变会导致基因组不稳定,产生新抗原,上调程序性死亡配体1(PD-L1)的表达,并与环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子(cGAS-STING)信号等信号传导相互作用。在此,我们综述了DDR途径的基础知识、DDR改变诱导基因组不稳定的机制、DDR改变对免疫系统的影响,以及DDR改变作为癌症免疫治疗中的生物标志物和治疗靶点的潜在应用。