Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Queensland, Australia.
Cancer Immunoregulation and Immunotherapy Laboratory, QIMR Berghofer Medical Research Institute, Queensland, Australia.
Nat Rev Clin Oncol. 2019 Mar;16(3):151-167. doi: 10.1038/s41571-018-0142-8.
Anticancer immunotherapies involving the use of immune-checkpoint inhibitors or adoptive cellular transfer have emerged as new therapeutic pillars within oncology. These treatments function by overcoming or relieving tumour-induced immunosuppression, thereby enabling immune-mediated tumour clearance. While often more effective and better tolerated than traditional and targeted therapies, many patients have innate or acquired resistance to immunotherapies. Cancer immunoediting is the process whereby the immune system can both constrain and promote tumour development, which proceeds through three phases termed elimination, equilibrium and escape. Throughout these phases, tumour immunogenicity is edited, and immunosuppressive mechanisms that enable disease progression are acquired. The mechanisms of resistance to immunotherapy seem to broadly overlap with those used by cancers as they undergo immunoediting to evade detection by the immune system. In this Review, we discuss how a deeper understanding of the mechanisms underlying the cancer immunoediting process can provide insight into the development of resistance to immunotherapies and the strategies that can be used to overcome such resistance.
癌症免疫疗法涉及使用免疫检查点抑制剂或过继性细胞转移，已成为肿瘤学中的新治疗支柱。这些治疗方法通过克服或缓解肿瘤引起的免疫抑制作用，从而实现免疫介导的肿瘤清除。虽然与传统和靶向治疗相比，免疫疗法通常更有效且更耐受，但许多患者对免疫疗法具有先天或获得性耐药性。癌症免疫编辑是指免疫系统既能限制又能促进肿瘤发展的过程，该过程通过三个阶段进行，分别称为消除、平衡和逃逸。在这些阶段中，肿瘤的免疫原性被编辑，并且获得了能够促进疾病进展的免疫抑制机制。对免疫疗法的耐药机制似乎与癌症在逃避免疫系统检测时所经历的免疫编辑中使用的机制广泛重叠。在这篇综述中，我们讨论了深入了解癌症免疫编辑过程背后的机制如何为免疫疗法耐药的发展提供见解，并讨论了可以用来克服这种耐药性的策略。
