Cancer therapy using immune checkpoint inhibitors (ICIs) is a promising clinical strategy for patients with multiple types of cancer. The expression of programmed cell death ligand-1 (PD-L1), an immune-suppressor ligand, in cancer cells is a factor that influences the efficacy of ICI therapy, particularly in the anti-programmed cell death protein-1 (PD-1)/PD-L1 antibody therapy. PD-L1 expression in cancer cells are associated with tumor mutation burden including microsatellite instability because the accumulation of mutations in the cancer genome can produce abnormal proteins via mutant mRNAs, resulting in neoantigen production and HLA-neoantigen complex presentation in cancer cells. HLA-neoantigen presentation promotes immune activity within tumor environment; therefore, known as hot tumor. Thus, as the fidelity of DNA repair affects the generation of genomic mutations, the status of DNA repair and signaling in cancer cells can be considered prior to ICI therapy. The Cancer Genome Atlas (TCGA) and The Cancer Immunome Atlas (TCIA) database analysis showed that tumor samples harboring mutations in any non-homologous end joining, homologous recombination, or DNA damage signaling genes exhibit high neoantigen levels. Alternatively, an urgent task is to understand how the DNA damage-associated cancer treatments change the status of immune activity in patients because multiple clinical trials on combination therapy are ongoing. Recent studies demonstrated that multiple pathways regulate PD-L1 expression in cancer cells. Here, we summarize the regulation of the immune response to ICI therapy, including PD-L1 expression, and also discuss the potential strategies to improve the efficacy of ICI therapy for poor responders from the viewpoint of DNA damage response before or after DNA damage-associated cancer treatment.

使用免疫检查点抑制剂（ICIs）的癌症治疗是多种癌症患者的有前途的临床策略。程序性细胞死亡配体-1（PD-L1）（一种免疫抑制配体）在癌细胞中的表达是影响ICI治疗功效的因素，尤其是在抗程序性细胞死亡蛋白-1（PD-1）中）/ PD-L1抗体疗法。癌细胞中PD-L1的表达与包括微卫星不稳定性在内的肿瘤突变负担有关，因为癌症基因组中突变的积累可通过突变mRNA产生异常蛋白质，从而导致癌细胞中产生新抗原和产生HLA-新抗原复合物。HLA-新抗原呈递促进肿瘤环境内的免疫活性；因此，被称为热肿瘤。从而，由于DNA修复的保真度会影响基因组突变的产生，因此可以在ICI治疗之前考虑癌细胞中DNA修复和信号传导的状态。癌症基因组图谱（TCGA）和癌症免疫组图谱（TCIA）数据库分析显示，携带任何非同源末端连接，同源重组或DNA损伤信号传导基因突变的肿瘤样品均显示高新抗原水平。另外，一项紧迫的任务是了解与DNA损伤相关的癌症治疗如何改变患者免疫活性的状态，因为有关联合治疗的多项临床试验正在进行中。最近的研究表明，多种途径调节癌细胞中PD-L1的表达。在这里，我们总结了对ICI治疗的免疫反应的调节，包括PD-L1表达，