Division of Medical Oncology, National Cancer Centre, Singapore 169610, Singapore.
Laboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore 169610, Singapore.
Int J Mol Sci. 2022 Nov 1;23(21):13356. doi: 10.3390/ijms232113356.
Genome instability and immune evasion are both defining hallmarks of cancer. Tumorigenesis is frequently initiated when there is DNA damage to a proto-oncogene or tumor suppressor gene and DNA repair mechanisms are lost or insufficient to correct the damage; immune evasion then prevents the host immune system from recognizing these transformed cells. Therapies targeting genomic instability and immune evasion have been effectively used to treat cancer. Genotoxic therapies such as chemoradiation have been employed in cancer treatments for several decades, while immunotherapy is a relatively new class of cancer therapy that has led to disease regression even in patients with advanced cancer. Several recent studies have shown synergy between both classes of therapy targeting these two defining hallmarks of cancer, and different mechanisms are proposed to be involved. Here, we review the different classes of DNA damage, their links to cancer, and their contribution to immunotherapy responses, as well as the different models that are currently being used to study tumor-immune interactions.
基因组不稳定性和免疫逃逸都是癌症的标志性特征。当原癌基因或肿瘤抑制基因发生 DNA 损伤，而 DNA 修复机制丧失或不足以纠正损伤时，肿瘤发生通常就会启动；随后，免疫逃逸会阻止宿主免疫系统识别这些转化细胞。针对基因组不稳定性和免疫逃逸的治疗方法已被有效地用于治疗癌症。几十年来，化学放射疗法等遗传毒性疗法已被用于癌症治疗，而免疫疗法是一种相对较新的癌症治疗方法，即使在晚期癌症患者中，也能导致疾病消退。最近的几项研究表明，针对这两个癌症标志性特征的两种治疗方法具有协同作用，并且提出了不同的机制参与其中。在这里，我们回顾了不同类型的 DNA 损伤及其与癌症的联系，以及它们对免疫治疗反应的贡献，以及目前用于研究肿瘤免疫相互作用的不同模型。
