Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Prof. Egas Moniz, Lisboa, Portugal. Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom. Graduate Program in Areas of Basic and Applied Biology, Universidade do Porto, Porto, Portugal.
Blizard Institute, Barts and The London School of Medicine, Queen Mary University of London, London, United Kingdom.
Cancer Res. 2015 Mar 1;75(5):798-802. doi: 10.1158/0008-5472.CAN-14-3228. Epub 2015 Feb 6.
Tumor-infiltrating lymphocytes are key mediators of tumor immune surveillance and are important prognostic indicators in cancer progression. Among the various lymphocyte subsets implicated in protection against cancer are γδ T lymphocytes, which can kill tumor cells and secrete potent antitumor cytokines. By contrast, recent reports have revealed an unexpected series of protumor functions of γδ T cells in mouse models and human patients. In particular, specific γδ T-cell subsets are capable of recruiting immunosuppressive myeloid populations, inhibiting antitumor responses, and enhancing angiogenesis, thus promoting cancer progression. A common mediator of such functions appears to be the cytokine IL17, whose pathogenic effects can override the antitumor immune response orchestrated by IFNγ. Here, we review these studies and discuss their implications for the manipulation of γδ T cells in cancer immunotherapy.
肿瘤浸润淋巴细胞是肿瘤免疫监视的关键介质，也是癌症进展中重要的预后指标。在各种参与预防癌症的淋巴细胞亚群中，γδ T 淋巴细胞能够杀伤肿瘤细胞并分泌强效的抗肿瘤细胞因子。相比之下，最近的研究报告揭示了 γδ T 细胞在小鼠模型和人类患者中一系列出乎意料的促肿瘤功能。具体而言，特定的 γδ T 细胞亚群能够募集免疫抑制性髓系群体，抑制抗肿瘤反应，并促进血管生成，从而促进癌症进展。这种功能的一个常见介导者似乎是细胞因子 IL17，其致病作用可以超过 IFNγ 协调的抗肿瘤免疫反应。在这里，我们综述了这些研究，并讨论了它们对癌症免疫治疗中 γδ T 细胞操作的影响。
