Bedard Melissa, Salio Mariolina, Cerundolo Vincenzo
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Front Immunol. 2017 Dec 18;8:1829. doi: 10.3389/fimmu.2017.01829. eCollection 2017.
Invariant natural killer T (iNKT) cells are a distinct subset of innate-like lymphocytes bearing an invariant T-cell receptor, through which they recognize lipid antigens presented by monomorphic CD1d molecules. Upon activation, iNKT cells are capable of not only having a direct effector function but also transactivating NK cells, maturing dendritic cells, and activating B cells, through secretion of several cytokines and cognate TCR-CD1d interaction. Endowed with the ability to orchestrate an all-encompassing immune response, iNKT cells are critical in shaping immune responses against pathogens and cancer cells. In this review, we examine the critical role of iNKT cells in antitumor responses from two perspectives: (i) how iNKT cells potentiate antitumor immunity and (ii) how CD1d tumor cells may modulate their own expression of CD1d molecules. We further explore hypotheses to explain iNKT cell activation in the context of cancer and how the antitumor effects of iNKT cells can be exploited in different forms of cancer immunotherapy, including their role in the development of cancer vaccines.
不变自然杀伤T（iNKT）细胞是一类独特的固有样淋巴细胞亚群，其携带不变的T细胞受体，通过该受体识别由单态性CD1d分子呈递的脂质抗原。激活后，iNKT细胞不仅能够发挥直接效应功能，还能通过分泌多种细胞因子以及TCR-CD1d的同源相互作用来反式激活自然杀伤细胞、使树突状细胞成熟并激活B细胞。iNKT细胞具有协调全面免疫反应的能力，在塑造针对病原体和癌细胞的免疫反应中至关重要。在本综述中，我们从两个角度探讨iNKT细胞在抗肿瘤反应中的关键作用：（i）iNKT细胞如何增强抗肿瘤免疫力，以及（ii）CD1d肿瘤细胞如何调节其自身CD1d分子的表达。我们进一步探讨了一些假说，以解释癌症背景下iNKT细胞的激活，以及如何在不同形式的癌症免疫治疗中利用iNKT细胞的抗肿瘤作用，包括它们在癌症疫苗开发中的作用。
