The DNA damage response (DDR) fulfils essential roles to preserve genome integrity. Targeting the DDR in tumors has had remarkable success over the last decade, exemplified by the licensing of PARP inhibitors for cancer therapy. Recent studies suggest that the application of DDR inhibitors impacts on cellular innate and adaptive immune responses, wherein key DNA repair factors have roles in limiting chronic inflammatory signaling. Antitumor immunity plays an emerging part in cancer therapy, and extensive efforts have led to the development of immune checkpoint inhibitors overcoming immune suppressive signals in tumors. Here, we review the current understanding of the molecular mechanisms underlying DNA damage-triggered immune responses, including cytosolic DNA sensing via the cGAS/STING pathway. We highlight the implications of DDR components for therapeutic outcomes of immune checkpoint inhibitors or their use as biomarkers. Finally, we discuss the rationale for novel combinations of DDR inhibitors with antagonists of immune checkpoints and current hindrances limiting their broader therapeutic applications.

中文翻译：

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细胞对 DNA 损伤的反应与癌症免疫治疗之间的相互作用


DNA 损伤反应 (DDR) 在保护基因组完整性方面发挥着重要作用。在过去十年中，靶向肿瘤中的 DDR 取得了显着的成功，用于癌症治疗的 PARP 抑制剂的许可就是例证。最近的研究表明，DDR 抑制剂的应用会影响细胞先天性和适应性免疫反应，其中关键的 DNA 修复因子在限制慢性炎症信号传导中发挥作用。抗肿瘤免疫在癌症治疗中发挥着新兴作用，广泛的努力导致了免疫检查点抑制剂的开发，克服了肿瘤中的免疫抑制信号。在这里，我们回顾了目前对 DNA 损伤触发免疫反应分子机制的理解，包括通过 cGAS/STING 途径进行胞质 DNA 传感。我们强调 DDR 成分对免疫检查点抑制剂的治疗结果或其作为生物标志物的用途的影响。最后，我们讨论了 DDR 抑制剂与免疫检查点拮抗剂的新型组合的基本原理以及当前限制其更广泛治疗应用的障碍。