Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Eur J Immunol. 2021 Jan;51(1):17-26. doi: 10.1002/eji.201948402. Epub 2020 Dec 8.
γδ T cells can display a plethora of immune functions, but recent studies have highlighted their importance, in multiple disease models, as sources of the pro-inflammatory cytokines, IL-17A (IL-17), and IFN-γ. These are produced by distinct murine effector γδ T cell subsets that diverge during thymic γδ T cell development. Among the multiple roles these subsets play in peripheral tissues, a striking dichotomy has emerged at tumor sites: whereas IFN-γ γδ T cells inhibit tumor cell growth, IL-17 γδ T cells promote tumor progression and metastasis formation. In this review, we discuss the main lines of evidence, mostly from preclinical studies in mouse models, for this functional dichotomy in cancer immunity. We further highlight very recent advances in our understanding how metabolic sources and pathways can impact on the balance between IFN-γ and IL-17 γδ T cells in the tumor microenvironment, which opens a new exciting avenue to explore toward the application of γδ T cells in cancer immunotherapy.
γδ T 细胞可以表现出多种免疫功能，但最近的研究强调了它们在多种疾病模型中的重要性，因为它们是促炎细胞因子白细胞介素-17A（IL-17）和干扰素-γ（IFN-γ）的来源。这些细胞因子由在胸腺 γδ T 细胞发育过程中分化的不同的鼠效应 γδ T 细胞亚群产生。在这些亚群在外周组织中发挥的多种作用中，在肿瘤部位出现了一个显著的二分法：虽然 IFN-γ γδ T 细胞抑制肿瘤细胞生长，但 IL-17 γδ T 细胞促进肿瘤进展和转移形成。在这篇综述中，我们讨论了主要的证据，主要来自于小鼠模型的临床前研究，证明了癌症免疫中的这种功能二分法。我们还强调了最近在我们对代谢来源和途径如何影响肿瘤微环境中 IFN-γ 和 IL-17 γδ T 细胞之间平衡的理解方面的进展，这为探索 γδ T 细胞在癌症免疫治疗中的应用开辟了一个令人兴奋的新途径。
