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黏膜相关恒定 T 细胞在癌症中的双重作用、复杂相互作用和治疗潜力。

Mucosal-associated invariant T cells in cancer: dual roles, complex interactions and therapeutic potential.

机构信息

Human Immunology Laboratory, Acibadem University School of Medicine, Istanbul, Türkiye.

Jackson Laboratory for Genomic Medicine, Farmington, CT, United States.

出版信息

Front Immunol. 2024 Mar 13;15:1369236. doi: 10.3389/fimmu.2024.1369236. eCollection 2024.

Abstract

Mucosal-associated invariant T (MAIT) cells play diverse roles in cancer, infectious diseases, and immunotherapy. This review explores their intricate involvement in cancer, from early detection to their dual functions in promoting inflammation and mediating anti-tumor responses. Within the solid tumor microenvironment (TME), MAIT cells can acquire an 'exhausted' state and secrete tumor-promoting cytokines. On the other hand, MAIT cells are highly cytotoxic, and there is evidence that they may have an anti-tumor immune response. The frequency of MAIT cells and their subsets has also been shown to have prognostic value in several cancer types. Recent innovative approaches, such as programming MAIT cells with chimeric antigen receptors (CARs), provide a novel and exciting approach to utilizing these cells in cell-based cancer immunotherapy. Because MAIT cells have a restricted T cell receptor (TCR) and recognize a common antigen, this also mitigates potential graft-versus-host disease (GVHD) and opens the possibility of using allogeneic MAIT cells as off-the-shelf cell therapies in cancer. Additionally, we outline the interactions of MAIT cells with the microbiome and their critical role in infectious diseases and how this may impact the tumor responses of these cells. Understanding these complex roles can lead to novel therapeutic strategies harnessing the targeting capabilities of MAIT cells.

摘要

黏膜相关恒定 T(MAIT)细胞在癌症、传染病和免疫治疗中发挥着多样化的作用。这篇综述探讨了它们在癌症中的复杂作用,从早期检测到促进炎症和介导抗肿瘤反应的双重功能。在实体瘤微环境(TME)中,MAIT 细胞可获得“衰竭”状态并分泌促进肿瘤的细胞因子。另一方面,MAIT 细胞具有高度细胞毒性,有证据表明它们可能具有抗肿瘤免疫反应。MAIT 细胞及其亚群的频率也被证明在几种癌症类型中具有预后价值。最近的创新方法,如用嵌合抗原受体(CAR)对 MAIT 细胞进行编程,为利用这些细胞进行基于细胞的癌症免疫治疗提供了一种新颖而令人兴奋的方法。因为 MAIT 细胞具有受限的 T 细胞受体(TCR)并识别共同抗原,这也减轻了潜在的移植物抗宿主病(GVHD)的风险,并为使用同种异体 MAIT 细胞作为现成的细胞疗法治疗癌症开辟了可能性。此外,我们概述了 MAIT 细胞与微生物组的相互作用及其在传染病中的关键作用,以及这如何影响这些细胞对肿瘤的反应。了解这些复杂的作用可以导致新的治疗策略,利用 MAIT 细胞的靶向能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c4c/10965779/e4536775312a/fimmu-15-1369236-g001.jpg

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