Synthetic glycolipid activators of natural killer T cells as immunotherapeutic agents.
Synthetic glycolipid activators of natural killer T cells as immunotherapeutic agents.
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DOI：
10.1038/cti.2016.14
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发表时间：
2016-04
影响因子：
5.8
通讯作者：
Porcelli SA
中科院分区：
文献类型：
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作者：
Carreño LJ;Saavedra-Ávila NA;Porcelli SA
已经发现某些类型的糖脂具有显著的免疫调节特性，这是由于它们能够以极其广泛的免疫效应特性激活特异性T淋巴细胞群。最广泛研究的糖脂反应性T细胞被称为不变的自然杀伤T（iNKT）细胞。这些细胞的抗原受体特异性识别某些糖脂，最显著的是由主要组织相容性复合物I类分子CD 1d呈递的具有α-异头单糖的鞘糖脂。一旦被激活，iNKT细胞可以分泌多种促炎和抗炎细胞因子来调节先天性和适应性免疫反应。因此，糖脂介导的iNKT细胞活化已被探索用于多种疾病状态的免疫治疗，包括癌症和一系列感染。在这篇综述中，我们讨论了iNKT细胞的合成糖脂激活剂的设计，它们对适应性免疫反应的影响，以及它们用于调节iNKT细胞反应以提高对感染和癌症的免疫力。还讨论了将临床前动物研究结果转化为人类研究结果的当前挑战。
Certain types of glycolipids have been found to have remarkable immunomodulatory properties as a result of their ability to activate specific T lymphocyte populations with an extremely wide range of immune effector properties. The most extensively studied glycolipid reactive T cells are known as invariant natural killer T (iNKT) cells. The antigen receptors of these cells specifically recognize certain glycolipids, most notably glycosphingolipids with α-anomeric monosaccharides, presented by the major histocompatibility complex class I-like molecule CD1d. Once activated, iNKT cells can secrete a very diverse array of pro- and anti-inflammatory cytokines to modulate innate and adaptive immune responses. Thus, glycolipid-mediated activation of iNKT cells has been explored for immunotherapy in a variety of disease states, including cancer and a range of infections. In this review, we discuss the design of synthetic glycolipid activators for iNKT cells, their impact on adaptive immune responses and their use to modulate iNKT cell responses to improve immunity against infections and cancer. Current challenges in translating results from preclinical animal studies to humans are also discussed.