Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Institute of Cancer Sciences, University of Glasgow and Cancer Research UK Beatson Institute, Glasgow, UK.
Nat Rev Cancer. 2019 Jul;19(7):392-404. doi: 10.1038/s41568-019-0153-5.
The potential of cancer immunotherapy relies on the mobilization of immune cells capable of producing antitumour cytokines and effectively killing tumour cells. These are major attributes of γδ T cells, a lymphoid lineage that is often underestimated despite its major role in tumour immune surveillance, which has been established in a variety of preclinical cancer models. This situation notwithstanding, in particular instances the tumour microenvironment seemingly mobilizes γδ T cells with immunosuppressive or tumour-promoting functions, thus emphasizing the importance of regulating γδ T cell responses in order to realize their translation into effective cancer immunotherapies. In this Review we outline both seminal work and recent advances in our understanding of how γδ T cells participate in tumour immunity and how their functions are regulated in experimental models of cancer. We also discuss the current strategies aimed at maximizing the therapeutic potential of human γδ T cells, on the eve of their exploration in cancer clinical trials that may position them as key players in cancer immunotherapy.
癌症免疫疗法的潜力依赖于能够产生抗肿瘤细胞因子并有效杀伤肿瘤细胞的免疫细胞的动员。这些都是 γδ T 细胞的主要特征，尽管 γδ T 细胞在肿瘤免疫监视中发挥着重要作用，但它常常被低估，这在多种临床前癌症模型中已经得到证实。尽管如此，在某些特定情况下，肿瘤微环境似乎动员了具有免疫抑制或促进肿瘤生长功能的 γδ T 细胞，因此强调了调节 γδ T 细胞反应的重要性，以便将其转化为有效的癌症免疫疗法。在这篇综述中，我们概述了 γδ T 细胞如何参与肿瘤免疫以及它们在癌症实验模型中的功能如何被调控的开创性工作和最新进展。我们还讨论了旨在最大限度地发挥人类 γδ T 细胞治疗潜力的现有策略，这些策略即将在癌症临床试验中进行探索，这可能使它们成为癌症免疫治疗的关键参与者。
