CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
人类癌症中的 T 细胞耗竭
英文原题：T cell exhaustion in human cancers.
查看英文原题
T cell exhaustion in human cancers.
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中文摘要
T细胞耗竭是指T细胞由于持续抗原刺激而出现功能进行性受损的状态，其特征是免疫抑制性受体表达增加，但效应功能减弱、自我更新能力降低，以及表观遗传学、转录程序和代谢发生改变。T细胞耗竭是导致癌症免疫逃逸的主要原因之一，可营造支持肿瘤发展和转移扩散的环境。
此外，T细胞耗竭对当前癌症免疫治疗的疗效起着关键作用。本综述旨在全面阐述T细胞耗竭在癌症发生和进展中的作用。我们总结了参与T细胞耗竭的调控机制，包括转录因子、表观遗传和代谢重编程事件，以及多种微环境因素，如细胞因子、微生物和肿瘤自分泌物质。本文还讨论了T细胞耗竭对癌症免疫治疗带来的挑战，包括免疫检查点阻断（ICB）疗法和CAR-T 细胞疗法，强调了由于T细胞耗竭而在ICB疗法和CAR-T 疗法中遇到的障碍。
最后，本文概述了当前旨在逆转或缓解ICB和CAR-T 疗法中T细胞耗竭的治疗选择。这些治疗策略试图克服T细胞耗竭，并增强免疫疗法治疗肿瘤的有效性。
展开英文摘要原文
T cell exhaustion refers to a progressive state in which T cells become functionally impaired due to sustained antigenic stimulation, which is characterized by increased expression of immune inhibitory receptors, but weakened effector functions, reduced self-renewal capacity, altered epigenetics, transcriptional programme and metabolism. T cell exhaustion is one of the major causes leading to immune escape of cancer, creating an environment that supports tumor development and metastatic spread.
In addition, T cell exhaustion plays a pivotal role to the efficacy of current immunotherapies for cancer. This review aims to provide a comprehensive view of roles of T cell exhaustion in cancer development and progression.
We summerized the regulatory mechanisms that involved in T cell exhaustion, including transcription factors, epigenetic and metabolic reprogramming events, and various microenvironmental factors such as cytokines, microorganisms, and tumor autocrine substances.
The paper also discussed the challenges posed by T cell exhaustion to cancer immunotherapies, including immune checkpoint blockade (ICB) therapies and chimeric antigen receptor T cell (CAR-T) therapy, highlightsing the obstacles encountered in ICB therapies and CAR-T therapies due to T cell exhaustion.
Finally, the article provides an overview of current therapeutic options aimed to reversing or alleviating T cell exhaustion in ICB and CAR-T therapies. These therapeutic approaches seek to overcome T cell exhaustion and enhance the effectiveness of immunotherapies in treating tumors.
论文信息
- 作者
- Kang K、Lin X、Chen P、Liu H、Liu F、Xiong W、Li G、Yi M
- 第一作者单位
- Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410008, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410078, Hunan, China.China
- 通讯作者单位
- Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan, China; The Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410008, Hunan, China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha 410078, Hunan, China; FuRong Laboratory, Changsha 410078, Hunan, China. Electronic address: xiangbolin@csu.edu.cn.China
- 文献类型
- 综述 · 非美国政府资助研究
- 期刊
- Biochimica et biophysica acta. Reviews on cancer2024 Sep
- 原文标识
- PubMed 39089484 · DOI 10.1016/j.bbcan.2024.189162