[抗肿瘤免疫反应中的CD8+ T细胞]
[CD8+ T Cells in Anti-Tumor Immune Response].
作者信息
Ohta Shigeki, Kawakami Yutaka
机构信息
Dept. of Immunology, School of Medicine, International University of Health and Welfare.
出版信息
Gan To Kagaku Ryoho. 2025 Jul;52(7):485-491.
The cancer-immunity cycle has been proposed, and immunotherapeutic approaches, such as vaccines using self-antigens and adjuvant, have been employed for a long time, but their therapeutic effects have been limited. However, recent studies have demonstrated that immune checkpoint inhibitors(ICIs)are able to achieve high therapeutic efficacy, in a variety of cancer types. Today, advances in multi-omics technologies, including single-cell RNA sequencing(scRNA-seq), spatial transcriptomics, and multicolor immunostaining technologies, have made it possible to analyze immune cell dynamics at the single-cell level in a greater detail. While CD8+ T cells play a central role in the antitumor immune response, recent findings have revealed the existence of various subsets within the CD8+ T cell population. During the research on T cell exhaustion, the in vivo dynamics of T progenitor exhausted cells(Tpex cells)/stem cell memory T cells(TSCM)have also been elucidated. Tpex/TSCM cells are present in tumor-draining lymph nodes and within tumors and have reported to be an important target for ICIs. Furthermore, interactions between CD4+ T cells, dendritic cells(DCs), B cells, and CD8+ T cells within the tumor microenvironment are crucial for the induction of cytotoxic CD8+ effector T cells. In human tumor tissues, cancer cells exhibit heterogeneous characteristics and the tumor microenvironment varies depending on cancer type, subtypes, and individual patients. To enhance the anti-tumor effects of CD8+ T cells in immunotherapy, it is essential to achieve a more precise understanding of the in vivo dynamics of CD8+ T cells in each patient and to develop strategies for their effective intervention. This knowledge will then be applied to the development of vaccine therapies, combination immunotherapies, and cellular immunotherapy.
癌症免疫循环已被提出,免疫治疗方法,如使用自身抗原和佐剂的疫苗,已经应用了很长时间,但其治疗效果有限。然而,最近的研究表明,免疫检查点抑制剂(ICIs)能够在多种癌症类型中实现高治疗效果。如今,包括单细胞RNA测序(scRNA-seq)、空间转录组学和多色免疫染色技术在内的多组学技术的进步,使得在单细胞水平上更详细地分析免疫细胞动态成为可能。虽然CD8+T细胞在抗肿瘤免疫反应中起核心作用,但最近的研究发现揭示了CD8+T细胞群体中存在各种亚群。在对T细胞耗竭的研究中,也阐明了T祖细胞耗竭细胞(Tpex细胞)/干细胞记忆T细胞(TSCM)的体内动态。Tpex/TSCM细胞存在于肿瘤引流淋巴结和肿瘤内,据报道是ICIs的重要靶点。此外,肿瘤微环境中CD4+T细胞、树突状细胞(DCs)、B细胞和CD8+T细胞之间的相互作用对于诱导细胞毒性CD8+效应T细胞至关重要。在人类肿瘤组织中,癌细胞表现出异质性特征,肿瘤微环境因癌症类型、亚型和个体患者而异。为了增强免疫治疗中CD8+T细胞的抗肿瘤作用,必须更精确地了解每个患者体内CD8+T细胞的动态,并制定有效的干预策略。这些知识随后将应用于疫苗治疗、联合免疫治疗和细胞免疫治疗的开发。