Department of Pathology, Duke University Medical Center, Durham, NC, United States.
Duke Medical School, Duke University Medical Center, Durham, NC, United States.
Front Immunol. 2021 Nov 18;12:777073. doi: 10.3389/fimmu.2021.777073. eCollection 2021.
Successful cancer immunotherapies rely on a replete and functional immune compartment. Within the immune compartment, T cells are often the effector arm of immune-based strategies due to their potent cytotoxic capabilities. However, many tumors have evolved a variety of mechanisms to evade T cell-mediated killing. Thus, while many T cell-based immunotherapies, such as immune checkpoint inhibition (ICI) and chimeric antigen receptor (CAR) T cells, have achieved considerable success in some solid cancers and hematological malignancies, these therapies often fail in solid tumors due to tumor-imposed T cell dysfunctions. These dysfunctional mechanisms broadly include reduced T cell access into and identification of tumors, as well as an overall immunosuppressive tumor microenvironment that elicits T cell exhaustion. Therefore, novel, rational approaches are necessary to overcome the barriers to T cell function elicited by solid tumors. In this review, we will provide an overview of conventional immunotherapeutic strategies and the various barriers to T cell anti-tumor function encountered in solid tumors that lead to resistance. We will also explore a sampling of emerging strategies specifically aimed to bypass these tumor-imposed boundaries to T cell-based immunotherapies.
成功的癌症免疫疗法依赖于丰富和功能正常的免疫环境。在免疫环境中，T 细胞由于其强大的细胞毒性能力，通常是免疫策略的效应臂。然而，许多肿瘤已经进化出多种机制来逃避 T 细胞介导的杀伤。因此，虽然许多基于 T 细胞的免疫疗法，如免疫检查点抑制（ICI）和嵌合抗原受体（CAR）T 细胞，在一些实体瘤和血液恶性肿瘤中取得了相当大的成功，但这些疗法在实体瘤中往往失败，因为肿瘤引起了 T 细胞功能障碍。这些功能障碍的机制包括 T 细胞进入和识别肿瘤的能力降低，以及整体免疫抑制的肿瘤微环境，导致 T 细胞衰竭。因此，需要新的、合理的方法来克服实体瘤引起的 T 细胞功能障碍。在这篇综述中，我们将概述传统的免疫治疗策略，以及实体瘤中遇到的各种阻碍 T 细胞抗肿瘤功能的障碍，从而导致耐药性。我们还将探讨一些新兴策略，这些策略专门旨在绕过这些肿瘤施加的 T 细胞免疫治疗的界限。
