Agenus Inc., Lexington, MA, United States.
Brigham & Women's Hospital, Harvard Medical School, Boston, MA, United States.
Front Immunol. 2018 Mar 2;9:384. doi: 10.3389/fimmu.2018.00384. eCollection 2018.
iNKT cells are a subset of innate-like T cells that utilize an invariant TCR alpha chain complexed with a limited repertoire of TCR beta chains to recognize specific lipid antigens presented by CD1d molecules. Because iNKT cells have an invariant TCR, they can be easily identified and targeted in both humans and mice via standard reagents, making this a population of T cells that has been well characterized. iNKT cells are some of the first cells to respond during an infection. By making different types of cytokines in response to different infection stimuli, iNKT cells help determine what kind of immune response then develops. It has been shown that iNKT cells are some of the first cells to respond during infection with a pathogen and the type of cytokines that iNKT cells make help determine the type of immune response that develops in various situations. Indeed, along with immunity to pathogens, pre-clinical mouse studies have clearly demonstrated that iNKT cells play a critical role in tumor immunosurveillance. They can mediate anti-tumor immunity by direct recognition of tumor cells that express CD1d, and/or via targeting CD1d found on cells within the tumor microenvironment. Multiple groups are now working on manipulating iNKT cells for clinical benefit within the context of cancer and have demonstrated that targeting iNKT cells can have a therapeutic benefit in patients. In this review, we briefly introduce iNKT cells, then discuss preclinical data on roles of iNKT cells and clinical trials that have targeted iNKT cells in cancer patients. We finally discuss how future trials could be modified to further increase the efficacy of iNKT cell therapies, in particular CAR-iNKT and rTCR-iNKT cells.
iNKT 细胞是先天样 T 细胞的一个亚群，其利用不变的 TCRα 链与有限的 TCRβ 链组合，识别由 CD1d 分子呈递的特定脂质抗原。由于 iNKT 细胞具有不变的 TCR，它们可以通过标准试剂在人类和小鼠中被轻松识别和靶向，这使得它们成为一个已经得到充分表征的 T 细胞群体。iNKT 细胞是感染过程中最早响应的细胞之一。通过对不同感染刺激物产生不同类型的细胞因子，iNKT 细胞有助于确定随后发展的免疫反应类型。已经表明，iNKT 细胞是感染病原体时最早响应的细胞之一，iNKT 细胞产生的细胞因子类型有助于确定在各种情况下发展的免疫反应类型。事实上，除了对病原体的免疫外，临床前小鼠研究还清楚地表明，iNKT 细胞在肿瘤免疫监视中起着关键作用。它们可以通过直接识别表达 CD1d 的肿瘤细胞，或者通过靶向肿瘤微环境中的细胞上的 CD1d 来介导抗肿瘤免疫。多个研究小组目前正在研究操纵 iNKT 细胞以在癌症背景下获得临床益处，并证明靶向 iNKT 细胞可以在患者中产生治疗益处。在这篇综述中，我们简要介绍了 iNKT 细胞，然后讨论了 iNKT 细胞在癌症中的作用的临床前数据和针对癌症患者的 iNKT 细胞临床试验。我们最后讨论了如何修改未来的试验以进一步提高 iNKT 细胞疗法的疗效，特别是 CAR-iNKT 和 rTCR-iNKT 细胞。
