摘要
免疫治疗,尤其是免疫检查点抑制,已成为癌症治疗的重要手段。然而,大多数癌症中仅有少数患者对免疫检查点阻断有反应。随着对肿瘤免疫治疗认识的深入,DNA损伤与修复机制在肿瘤免疫逃逸中的作用愈发显著。基因组不稳定性和DNA损伤应答的缺陷,尤其是在放射治疗和化学治疗的背景下,能够增强免疫检查点阻断的疗效。尽管研究已取得积极进展,但如何精准地调控DNA损伤应答以及优化联合治疗策略,提高疗效和减少毒副作用,仍是未来研究的重点。本文详细讨论放射治疗和化学治疗等传统基因毒性治疗与免疫检查点阻断联合治疗策略的免疫调节机制,探讨干扰素基因刺激因子激动剂和DNA损伤应答抑制剂在联合治疗中的潜力,还提出基于DNA损伤应答靶向抑制与免疫治疗联合应用的新策略,强调了结合传统治疗和新型免疫调节策略以及开发生物标志物的重要性。
Immunotherapy,especially immune checkpoint inhibition,has become a crucial method in cancer treatment.However,only a minority of patients across most cancer types respond to immune checkpoint blockade.As our understanding of cancer immunotherapy deepens,the role of DNA damage and repair mechanisms in tumor immune evasion becomes increasingly significant.Studies have shown that genomic instability and defects in the DNA damage response,particularly in the context of radiation and chemotherapy,can enhance the efficacy of immune checkpoint blockade.Although current research has made positive strides,the precise regulation of DNA damage response and the optimization of combination therapy strategies to improve efficacy and reduce side effects remain key areas for future research.This article discussed in detail the immune modulation mechanisms of traditional genotoxic therapies such as radiotherapy and chemotherapy combined with immune checkpoint blockade,and explored the potentials for a stimulator of interferon gene agonists and DNA damage response inhibitors in combination therapy.Additionally,a new strategy was proposed based on a combined application of DNA damage response-targeted inhibition and immunotherapy,emphasizing the importance of integrating traditional treatments with novel immunomodulatory strategies and developing biomarkers.
作者
王琦
严俊芳
胡步荣
Wang Qi;Yan Junfang;Hu Burong(School of Public Health,Wenzhou Medical University,Wenzhou 325035,Zhejiang,China)
出处
《兰州大学学报（医学版）》
2024年第7期1-11,21,共12页
Journal of Lanzhou University（Medical Sciences）
基金
国家自然科学青年基金资助项目(82203981)
温州医科大学引进人才启动资助项目(QTJ20010)。
