免疫抑制性肿瘤微环境(TME)仍然是阻碍实施有效的针对固态癌症的免疫疗法的最普遍的障碍之一。主要由免疫抑制性肿瘤相关巨噬细胞(TAMs)和骨髓来源的抑制细胞(MDSCs)等组成,TME减弱免疫检查点阻断和过继细胞疗法的影响,要求一种能够治疗TME的新疗法。在这篇综述中,我们探讨了三种先天样T细胞亚群的潜力,不变自然杀手T(iNKT),粘膜相关不变T(MAIT)细胞,和γδT(γδT)细胞,显示固有的抗TAM/MDSC能力。表现出先天和适应性,先天样T细胞类型表达具有不同重组的亚群特异性TCR,形态学,和靶细胞识别,进一步补充了多种NK激活受体。NK活化受体和TCR活化均导致针对TME修复的靶向免疫抑制细胞的效应细胞毒性。此外,先天样T细胞表现出中等水平的肿瘤细胞杀伤,提供双重抗肿瘤和抗TAM/MDSC功能。这种潜在的抗肿瘤能力可以通过嵌合抗原受体(CAR)工程来进一步增强,以识别肿瘤特异性抗原以增强抗肿瘤靶向。与已建立的CAR-T细胞疗法相反,采用这些先天样细胞类型提供了增强的安全性,而没有移植物抗宿主病(GvHD)的风险,由于它们不识别错配的主要组织相容性复合体(MHC)分子,以便广泛使用,同种异体“现成的”癌症免疫疗法。
The immunosuppressive tumor microenvironment (TME) remains one of the most prevailing barriers obstructing the implementation of effective immunotherapy against solid-state cancers. Eminently composed of immunosuppressive tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) among others, the TME attenuates the effects of immune checkpoint blockade and adoptive cell therapies, mandating a novel therapy capable of TME remediation. In this review we explore the potential of three innate-like T cell subsets, invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT) cells, and gamma delta T (γδT) cells, that display an intrinsic anti-TAM/MDSC capacity. Exhibiting both innate and adaptive properties, innate-like T cell types express a subset-specific TCR with distinct recombination, morphology, and target cell recognition, further supplemented by a variety of NK activating receptors. Both NK activating receptor and TCR activation result in effector cell cytotoxicity against targeted immunosuppressive cells for TME remediation. In addition, innate-like T cells showcase moderate levels of tumor cell killing, providing dual antitumor and anti-TAM/MDSC function. This latent antitumor capacity can be further bolstered by chimeric antigen receptor (CAR) engineering for recognition of tumor specific antigens to enhance antitumor targeting. In contrast with established CAR-T cell therapies, adoption of these innate-like cell types provides an enhanced safety profile without the risk of graft versus host disease (GvHD), due to their non-recognition of mismatched major histocompatibility complex (MHC) molecules, for use as widely accessible, allogeneic \"off-the-shelf\" cancer immunotherapy.