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肿瘤中的干细胞样 CD8(+) T 细胞

英文原题:Stem-like CD8(+) T cells in cancer.

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Stem-like CD8(+) T cells in cancer.

PubMed 2024/08/15(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

干细胞样CD8+ T细胞(T SL)是具有优越持久性和抗肿瘤免疫力的免疫细胞亚群。它们为TCF1+PD-1+,对于肿瘤特异性CD8+ T细胞在检查点阻断免疫治疗应答中的扩增至关重要。在急性感染中,初始CD8+ T细胞分化为效应和记忆CD8+ T细胞;在癌症和慢性感染中,持续性抗原刺激可导致T细胞耗竭。近期研究强调了晚期功能失调(或耗竭)T细胞(T LD)——即TCF1-PD-1+——与自我更新的TCF1+PD-1+ T SL之间的二分关系,后者是前者的来源。TCF1+ T SL细胞被认为具有类似记忆T细胞群的干细胞样特性,并可分化为介导肿瘤控制的细胞毒性效应和短暂T细胞表型(T TE)。在这篇综述中,我们将讨论关于T SL形成和扩增研究的最新进展,以及在癌症背景下其分化和维持所需的独特微环境。

我们还将讨论生成这些细胞的潜在策略,及其在疫苗设计、免疫检查点阻断(ICB)和过继性T细胞治疗中增强干性的临床意义。

展开英文摘要原文

Stem-like CD8 + T cells (T SL ) are a subset of immune cells with superior persistence and antitumor immunity. They are TCF1 + PD-1 + and important for the expansion of tumor specific CD8 + T cells in response to checkpoint blockade immunotherapy. In acute infections, naïve CD8 + T cells differentiate into effector and memory CD8 + T cells; in cancer and chronic infections, persistent antigen stimulation can lead to T cell exhaustion.

Recent studies have highlighted the dichotomy between late dysfunctional (or exhausted) T cells (T LD ) that are TCF1 - PD-1 + and self-renewing TCF1 + PD-1 + T SL from which they derive. TCF1 + T SL cells are considered to have stem cell-like properties akin to memory T cell populations and can give rise to cytotoxic effector and transitory T cell phenotypes (T TE ) which mediate tumor control.

In this review, we will discuss recent advances made in research on the formation and expansion of T SL , as well as distinct niches required for their differentiation and maintenance in the setting of cancer.

We will also discuss potential strategies to generate these cells, with clinical implications for stemness enhancement in vaccine design, immune checkpoint blockade (ICB), and adoptive T cell therapies.

论文信息

作者
Steiner C、Denlinger N、Huang X、Yang Y
单位
Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States.United States
文献类型
综述
期刊
Frontiers in immunology2024
原文标识
PubMed 39211052 · DOI 10.3389/fimmu.2024.1426418