Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Adv Exp Med Biol. 2020;1224:53-62. doi: 10.1007/978-3-030-35723-8_4.
In the tumor microenvironment, CD8 T cells play a major role in tumor immunity. CD8 T cells differentiate to cytotoxic T cells, traffic into the tumor microenvironment, and exhibit cytotoxicity against tumor cells. These processes have both positive and negative effects. Enhancements in the cytotoxic activity of tumor antigen-specific cytotoxic T cells in the tumor microenvironment are crucial for the development of cancer immunotherapy. To achieve this, several immunotherapies, including cancer vaccines, T cells engineered to express chimeric antigen receptors (CAR T cells), and bispecific T-cell engagers (BiTEs), have been developed. In contrast to cancer vaccines, CAR T cells, and BiTEs, immune checkpoint inhibitors enhance the activity of cytotoxic T cells by inhibiting the negative regulators of T cells.The total number, type, and activity of tumor antigen-specific cytotoxic T cells in the tumor microenvironment need to be clarified, particularly for the development of companion diagnostics to identify patients for whom these therapies are effective. Therefore, technologies including TCR repertoire, single-cell, and T-cell cytotoxicity analyses using BiTEs have been developed.Based on these and future innovations, the generation of effective cancer immunotherapies is anticipated.
在肿瘤微环境中，CD8 T 细胞在肿瘤免疫中发挥着主要作用。CD8 T 细胞分化为细胞毒性 T 细胞，进入肿瘤微环境，并对肿瘤细胞表现出细胞毒性。这些过程既有积极的影响，也有消极的影响。增强肿瘤微环境中肿瘤抗原特异性细胞毒性 T 细胞的细胞毒性活性对于癌症免疫治疗的发展至关重要。为此，已经开发了几种免疫疗法，包括癌症疫苗、表达嵌合抗原受体（CAR T 细胞）的工程化 T 细胞以及双特异性 T 细胞衔接器（BiTE）。与癌症疫苗、CAR T 细胞和 BiTE 不同，免疫检查点抑制剂通过抑制 T 细胞的负调节剂来增强细胞毒性 T 细胞的活性。需要阐明肿瘤微环境中肿瘤抗原特异性细胞毒性 T 细胞的总数、类型和活性，特别是为了开发伴随诊断以识别这些疗法有效的患者。因此，已经开发了包括 TCR 库、单细胞和使用 BiTE 的 T 细胞细胞毒性分析在内的技术。基于这些和未来的创新，预计将产生有效的癌症免疫疗法。
