关键词： ATM, ataxia-telangiectasia mutated ATR, ataxia telangiectasia and Rad3 related BAP1, BRCA1-associated protein 1 BER, base excision repair BRAF, v-RAF murine sarcoma viral oncogene homologue B BRCA, breast cancer susceptibility gene CHEK, cell-cycle checkpoint kinase CHK1, checkpoint kinase 1 DAMP, damage-associated molecular patterns DDR, DNA damage response DNA damage response DNA repair DR, direct repair DSBs, double-strand breaks FDA, United State Food and Drug Administration GSK3β, glycogen synthase kinase 3β Genomic instability HMGB1, high mobility group box-1 HRR, homologous recombination repair ICI, immune checkpoint inhibitor IFNγ, interferon gamma IHC, immunohistochemistry IRF1, interferon regulatory factor 1 Immunotherapy JAK, Janus kinase MAD1, mitotic arrest deficient-like 1 MGMT, O6-methylguanine methyltransferase MLH1, MutL homolog 1 MMR, mismatch repair MNT, MAX network transcriptional repressor MSH2/6, MutS protein homologue-2/6 MSI, microsatellite instability MUTYH, MutY homolog MyD88, myeloid differentiation factor 88 NEK1, NIMA-related kinase 1 NER, nucleotide excision repair NGS, next generation sequencing NHEJ, nonhomologous end-joining NIMA, never-in-mitosis A NSCLC, non-small cell lung cancer ORR, objective response rate OS, overall survival PALB2, partner and localizer of BRCA2 PARP, poly-ADP ribose polymerase PCR, polymerase chain reaction PD-1 PD-1, programmed death 1 PD-L1 PD-L1, programmed death ligand 1 PFS, progression-free survival RAD51C, RAD51 homolog C RB1, retinoblastoma 1 RPA, replication protein A RSR, replication stress response SCNAs, somatic copy number alterations STAT, signal transducer and activator of transcription STING, stimulator of interferon genes TBK1, TANK-binding kinase 1 TILs, tumor-infiltrating lymphocytes TLR4, Toll-like receptor 4 TMB, tumor mutational burden TME, tumor microenvironment TP53, tumor protein P53 TRIF, Toll-interleukin 1 receptor domain-containing adaptor inducing INF-β Tumor microenvironment XRCC4, X-ray repair cross complementing protein 4 cGAS, cyclic GMP–AMP synthase cGAS–STING ssDNA, single-stranded DNA

来  源：   DOI：10.1016/j.apsb.2021.01.003   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
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.
摘要：
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。
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