基因组不稳定性仍然是癌症的有利特征,并促进恶性转化。DNA损伤反应(DDR)途径的改变允许基因组不稳定,产生新抗原,上调程序性死亡配体1(PD-L1)的表达,并与信号传导如干扰素基因的环GMP-AMP合酶-刺激物(cGAS-STING)信号传导相互作用。这里,我们回顾了DDR途径的基本知识,DDR改变引起的基因组不稳定性的机制,DDR改变对免疫系统的影响,以及DDR改变作为生物标志物和治疗靶点在癌症免疫治疗中的潜在应用。
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.