Immunotherapeutic strategies targeting natural killer T cell responses in cancer.

Immunotherapeutic strategies targeting natural killer T cell responses in cancer.
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DOI:
10.1007/s00251-016-0928-8
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发表时间:
2016-08
期刊:
影响因子:
3.2
通讯作者:
Webb TJ
Webb TJ
中科院分区:
医学4区
文献类型:
--
作者:
Shissler SC;Bollino DR;Tiper IV;Bates JP;Derakhshandeh R;Webb TJ

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自然杀伤T(NKT)细胞是连接先天免疫系统和获得性免疫系统的一种独特的淋巴细胞亚群。NKT细胞具有典型的αβT细胞受体,能够识别由非经典的I类主要组织相容性复合体分子CD1d呈递的自身和外源糖脂抗原。I型NKT细胞(称为不变NKT细胞)在小鼠和人中分别表达Vα14Jα18TCR和Vα24Jα18TCR。II型NKT细胞是CD1d限制性T细胞,表达一组更多样化的TcRα链。这两种类型的NKT细胞往往发挥相反的作用,特别是在肿瘤免疫方面,II型细胞通常抑制肿瘤免疫,而I型NKT细胞可以增强抗肿瘤免疫反应。在这篇综述中,我们重点介绍NKT细胞在癌症中的作用。我们讨论了它们的效应和抑制功能,并描述了利用其强大的抗肿瘤效应功能的治疗策略进行的临床前和临床研究,最后讨论了下一步利用NKT细胞靶向治疗癌症的可能步骤。
Natural killer T (NKT) cells are a unique subset of lymphocytes that bridge the innate and adaptive immune system. NKT cells possess a classic αβ T-cell receptor (TCR) that is able to recognize self and foreign glycolipid antigens presented by the nonclassical class I major histocompatibility complex (MHC) molecule, CD1d. Type I NKT cells (referred to as invariant NKT cells) express a semi-invariant Vα14Jα18 TCR in mice and Vα24Jα18 TCR in humans. Type II NKT cells are CD1d-restricted T cells that express a more diverse set of TCR α chains. The two types of NKT cells often exert opposing effects especially in tumor immunity, where Type II cells generally suppress tumor immunity while Type I NKT cells can enhance antitumor immune responses. In this review, we focus on the role of NKT cells in cancer. We discuss their effector and suppressive functions, as well as describe preclinical and clinical studies utilizing therapeutic strategies focused on harnessing their potent anti-tumor effector functions, and conclude with a discussion on potential next steps for the utilization of NKT cell targeted therapies for the treatment of cancer.
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