CD8+ T细胞在抗肿瘤免疫应答中的作用

Q4 Medicine
Shigeki Ohta, Yutaka Kawakami
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引用次数: 0

摘要

癌症-免疫周期已被提出,免疫治疗方法,如使用自身抗原和佐剂的疫苗,已被采用了很长时间,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)能够在各种癌症类型中实现高治疗效果。如今,多组学技术的进步,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,使得在单细胞水平上更详细地分析免疫细胞动力学成为可能。虽然CD8+ T细胞在抗肿瘤免疫反应中起着核心作用,但最近的研究结果揭示了CD8+ T细胞群中存在各种亚群。在T细胞耗竭的研究中,也阐明了T祖耗竭细胞(Tpex细胞)/干细胞记忆T细胞(TSCM)的体内动力学。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(dc)、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CD8+ T细胞在免疫治疗中的抗肿瘤作用,有必要更精确地了解每个患者体内CD8+ T细胞的动态,并制定有效干预的策略。这些知识随后将应用于疫苗疗法、联合免疫疗法和细胞免疫疗法的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[CD8+ T Cells in Anti-Tumor Immune Response].

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.

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