Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nat Rev Cancer. 2019 Mar;19(3):133-150. doi: 10.1038/s41568-019-0116-x.
Checkpoint inhibitor-based immunotherapies that target cytotoxic T lymphocyte antigen 4 (CTLA4) or the programmed cell death 1 (PD1) pathway have achieved impressive success in the treatment of different cancer types. Yet, only a subset of patients derive clinical benefit. It is thus critical to understand the determinants driving response, resistance and adverse effects. In this Review, we discuss recent work demonstrating that immune checkpoint inhibitor efficacy is affected by a combination of factors involving tumour genomics, host germline genetics, PD1 ligand 1 (PDL1) levels and other features of the tumour microenvironment, as well as the gut microbiome. We focus on recently identified molecular and cellular determinants of response. A better understanding of how these variables cooperate to affect tumour-host interactions is needed to optimize the implementation of precision immunotherapy.
基于细胞毒性 T 淋巴细胞相关抗原 4（CTLA4）或程序性死亡受体 1（PD1）通路的免疫检查点抑制剂在治疗不同癌症类型方面取得了令人瞩目的成功。然而，只有一部分患者从中获得临床获益。因此，了解驱动反应、耐药性和不良反应的决定因素至关重要。在这篇综述中，我们讨论了最近的研究工作，这些工作表明，免疫检查点抑制剂的疗效受到多种因素的影响，包括肿瘤基因组学、宿主种系遗传学、PD1 配体 1（PDL1）水平和肿瘤微环境的其他特征，以及肠道微生物组。我们重点关注最近确定的反应的分子和细胞决定因素。需要更好地了解这些变量如何合作影响肿瘤-宿主相互作用，以优化精准免疫治疗的实施。
