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为 T 细胞抗肿瘤免疫提供能量:氨基酸代谢再审视

英文原题:Fueling T-cell Antitumor Immunity: Amino Acid Metabolism Revisited.

查看英文原题

Fueling T-cell Antitumor Immunity: Amino Acid Metabolism Revisited.

PubMed 2021/10/29(内容时间) Cancer Immunol Res Q1 · IF 7.9(JCR 2025)

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中文摘要

T细胞是消除恶性肿瘤的关键角色。过继转移肿瘤抗原特异性T细胞和免疫检查点阻断已在临床上产生了持久的抗肿瘤反应,但并非所有患者初始即有反应,而一些有反应的患者最终会出现肿瘤进展。因此,需要新的方法来增强免疫治疗的效用。T细胞的激活和分化状态在转录、表观遗传和代谢水平上受到严格控制。氨基酸参与T细胞抗肿瘤免疫的多个步骤,包括T细胞激活、增殖、效应功能、记忆形成以及功能性耗竭。在这篇综述中,我们简要讨论了氨基酸代谢如何与T细胞命运决定相关联,并总结了肿瘤微环境中氨基酸剥夺或某些氨基酸代谢物积累如何削弱T细胞功能。此外,我们讨论了通过调节T细胞内源性或外源性的氨基酸代谢来实现治疗效果的潜在免疫治疗策略。

展开英文摘要原文

T cells are the key players in eliminating malignant tumors. Adoptive transfer of tumor antigen-specific T cells and immune checkpoint blockade has yielded durable antitumor responses in the clinic, but not all patients respond initially and some that do respond eventually have tumor progression.

Thus, new approaches to enhance the utility of immunotherapy are needed. T-cell activation and differentiation status are tightly controlled at the transcriptional, epigenetic, and metabolic levels. Amino acids are involved in multiple steps of T-cell antitumor immunity, including T-cell activation, proliferation, effector function, memory formation as well as functional exhaustion.

In this review, we briefly discuss how amino acid metabolism is linked to T-cell fate decisions and summarize how amino acid deprivation or accumulation of certain amino acid metabolites within the tumor microenvironment diminishes T-cell functionality.

Furthermore, we discuss potential strategies for immunotherapy via modulating amino acid metabolism either in T cells intrinsically or extrinsically to achieve therapeutic efficacy.

论文信息

作者
Han C、Ge M、Ho PC、Zhang L
第一作者单位
CAMS Key Laboratory of Synthetic Biology Regulatory Elements, Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.China
通讯作者单位
CAMS Key Laboratory of Synthetic Biology Regulatory Elements, Institute of Systems Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. zlj@ism.cams.cn ping-chih.ho@unil.ch.China
文献类型
非美国政府资助研究 · 综述
期刊
Cancer immunology research2021 Dec
原文标识
PubMed 34716193 · DOI 10.1158/2326-6066.CIR-21-0459