Duke University Medical Center, Durham, NC 27710, United States.
Duke Cancer Institute, Durham, NC 27710, United States.
Adv Drug Deliv Rev. 2021 Nov;178:113962. doi: 10.1016/j.addr.2021.113962. Epub 2021 Sep 1.
Although PD-1 and CTLA-4 inhibitors have proven successful in a range of malignancies, there are subsets of patients that do not respond to these agents due to upregulation of adaptive and innate resistance mechanisms by the tumor and its surrounding microenvironment. As new immunotherapeutic strategies are developed, there is a need for rational implementation of novel immunotherapy combinations that target complementary mechanisms of immunotherapy resistance intrinsic to each patient and tumor type. In this short review, we cover mechanisms by which tumors evade the immune system, as well as summarize available clinical data on emerging therapeutic agents that target these defense mechanisms. Rational implementation of combination immunotherapy targeting patient- and malignancy-specific immune evasion mechanisms may thus lead to enhanced response rates and allow immunotherapy to be effective even in tumors that are historically considered poorly responsive to immunotherapy.
尽管 PD-1 和 CTLA-4 抑制剂已被证明在多种恶性肿瘤中有效，但由于肿瘤及其周围微环境中适应性和先天耐药机制的上调，仍有一部分患者对这些药物没有反应。随着新的免疫治疗策略的发展，需要合理地实施针对每个患者和肿瘤类型固有免疫治疗耐药的互补机制的新型免疫治疗组合。在这篇简短的综述中，我们涵盖了肿瘤逃避免疫系统的机制，并总结了靶向这些防御机制的新型治疗药物的现有临床数据。针对患者和肿瘤特异性免疫逃逸机制的联合免疫治疗的合理实施，可能会提高缓解率，并使免疫治疗在那些既往认为对免疫治疗反应不佳的肿瘤中也能有效。
