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凋亡:T 细胞免疫治疗中的双面神

英文原题:Apoptosis: a Janus bifrons in T-cell immunotherapy.

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Apoptosis: a Janus bifrons in T-cell immunotherapy.

PubMed 2023/04/01(内容时间) J Immunother Cancer Q1 · IF 11.7(JCR 2025)

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中文摘要

免疫疗法已经彻底改变了癌症的治疗。特别是免疫检查点阻断、双特异性抗体和过继性T细胞转移,在血液系统恶性肿瘤和实体癌中产生了前所未有的临床结果。虽然基于T细胞的免疫疗法具有多种作用机制,但其最终目标是实现癌细胞的凋亡。毫不意外,凋亡逃逸是癌症生物学的一个关键特征。因此,增强癌细胞对凋亡的敏感性代表了改善癌症免疫治疗临床结果的关键策略。事实上,除了促进T细胞凋亡和逃逸治疗的特征外,癌细胞还具有多种抵抗凋亡的内在机制。然而,凋亡是一把双刃剑:当它发生在T细胞中时,它代表了免疫疗法失败的关键机制。本综述将总结近期通过增加癌细胞凋亡易感性来增强基于T细胞的免疫疗法的努力,并讨论凋亡在调节肿瘤微环境中细胞毒性T淋巴细胞存活中的作用以及克服这一问题的潜在策略。

展开英文摘要原文

Immunotherapy has revolutionized the treatment of cancer. In particular, immune checkpoint blockade, bispecific antibodies, and adoptive T-cell transfer have yielded unprecedented clinical results in hematological malignancies and solid cancers. While T cell-based immunotherapies have multiple mechanisms of action, their ultimate goal is achieving apoptosis of cancer cells. Unsurprisingly, apoptosis evasion is a key feature of cancer biology.

Therefore, enhancing cancer cells' sensitivity to apoptosis represents a key strategy to improve clinical outcomes in cancer immunotherapy. Indeed, cancer cells are characterized by several intrinsic mechanisms to resist apoptosis, in addition to features to promote apoptosis in T cells and evade therapy.

However, apoptosis is double-faced: when it occurs in T cells, it represents a critical mechanism of failure for immunotherapies. This review will summarize the recent efforts to enhance T cell-based immunotherapies by increasing apoptosis susceptibility in cancer cells and discuss the role of apoptosis in modulating the survival of cytotoxic T lymphocytes in the tumor microenvironment and potential strategies to overcome this issue.

论文信息

作者
Lee YG、Yang N、Chun I、Porazzi P、Carturan A、Paruzzo L、Sauter CT、Guruprasad P
第一作者单位
Division of Hematology and Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.United States
通讯作者单位
Division of Hematology and Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA mruella@upenn.edu.United States
文献类型
综述 · 美国 NIH 资助研究 · 非美国政府资助研究
期刊
Journal for immunotherapy of cancer2023 Apr
原文标识
PubMed 37055217 · DOI 10.1136/jitc-2022-005967