NIHR Biomedical Research Centre, School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Biological Sciences, University of Southampton, Southampton, United Kingdom.
Front Immunol. 2023 Apr 19;14:1176724. doi: 10.3389/fimmu.2023.1176724. eCollection 2023.
Invariant natural killer T (iNKT) cells are a unique T lymphocyte population expressing semi-invariant T cell receptors (TCRs) that recognise lipid antigens presented by CD1d. iNKT cells exhibit potent anti-tumour activity through direct killing mechanisms and indirectly through triggering the activation of other anti-tumour immune cells. Because of their ability to induce potent anti-tumour responses, particularly when activated by the strong iNKT agonist αGalCer, they have been the subject of intense research to harness iNKT cell-targeted immunotherapies for cancer treatment. However, despite potent anti-tumour efficacy in pre-clinical models, the translation of iNKT cell immunotherapy into human cancer patients has been less successful. This review provides an overview of iNKT cell biology and why they are of interest within the context of cancer immunology. We focus on the iNKT anti-tumour response, the seminal studies that first reported iNKT cytotoxicity, their anti-tumour mechanisms, and the various described subsets within the iNKT cell repertoire. Finally, we discuss several barriers to the successful utilisation of iNKT cells in human cancer immunotherapy, what is required for a better understanding of human iNKT cells, and the future perspectives facilitating their exploitation for improved clinical outcomes.
天然不变自然杀伤 T(iNKT)细胞是一种独特的 T 淋巴细胞群体，表达半不变 T 细胞受体(TCRs)，可识别 CD1d 呈递的脂质抗原。iNKT 细胞通过直接杀伤机制和间接触发其他抗肿瘤免疫细胞的激活，表现出强大的抗肿瘤活性。由于它们能够诱导强烈的抗肿瘤反应，特别是当它们被强烈的 iNKT 激动剂 αGalCer 激活时，它们一直是利用 iNKT 细胞靶向免疫疗法治疗癌症的强烈研究主题。然而，尽管在临床前模型中具有强大的抗肿瘤功效，但 iNKT 细胞免疫疗法在人类癌症患者中的转化效果并不理想。
这篇综述概述了 iNKT 细胞生物学，以及为什么它们在癌症免疫学背景下具有重要意义。我们重点介绍了 iNKT 的抗肿瘤反应、首次报道 iNKT 细胞细胞毒性的开创性研究、它们的抗肿瘤机制，以及 iNKT 细胞库中描述的各种亚群。最后，我们讨论了在人类癌症免疫治疗中成功利用 iNKT 细胞的几个障碍，以及更好地理解人类 iNKT 细胞所需的条件，以及促进其利用以改善临床结果的未来前景。
