[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.

DOI:
Abstract

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.

摘要

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。

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