Deligianni Elisavet, Papanikolaou Christina, Terpos Evangelos, Souliotis Vassilis L
Institute of Chemical Biology, National Hellenic Research Foundation, 116 35 Athens, Greece.
Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 115 28 Athens, Greece.
Int J Mol Sci. 2025 Jun 18;26(12):5849. doi: 10.3390/ijms26125849.
The DNA-damage response (DDR) network and the immune system are significant mechanisms linked to the normal functioning of living organisms. Extensive observations suggest that agents that damage the DNA can boost immunity in various ways, some of which may be useful for immunotherapeutic applications. Indeed, the immune system can be activated by the DDR network through a number of different mechanisms, such as via (a) an increase in the tumor neoantigen burden, (b) the induction of the stimulator of interferon genes pathway, (c) the triggering of immunogenic cell death, (d) an increase in antigen presentation as a result of the augmented expression of the major histocompatibility complex type I molecule, (e) modification of the cytokine milieu in the tumor microenvironment, and (f) altered expression of the programmed cell death ligand-1. Together, the DDR network may improve the effect of immunostimulatory anticancer agents and provide a basis for devising more efficient treatment strategies, such as combinatorial therapies of DDR targeting drugs and immunomodulators. Here, the molecular mechanisms underlying the immune system's activation by DDR are summarized, along with some of their possible uses in cancer treatment.
DNA损伤反应（DDR）网络和免疫系统是与生物体正常功能相关的重要机制。大量观察表明，损伤DNA的因子可通过多种方式增强免疫力，其中一些方式可能对免疫治疗应用有用。事实上，DDR网络可通过多种不同机制激活免疫系统，例如：（a）肿瘤新抗原负荷增加；（b）干扰素基因刺激因子途径的诱导；（c）免疫原性细胞死亡的触发；（d）由于主要组织相容性复合体I类分子表达增加导致抗原呈递增加；（e）肿瘤微环境中细胞因子环境的改变；以及（f）程序性细胞死亡配体-1表达的改变。总之，DDR网络可能会提高免疫刺激抗癌药物的效果，并为设计更有效的治疗策略提供基础，例如DDR靶向药物与免疫调节剂的联合治疗。在此，总结了DDR激活免疫系统的分子机制及其在癌症治疗中的一些可能用途。
