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CD8 T 细胞耗竭与癌症免疫治疗。

CD8 T cell exhaustion and cancer immunotherapy.

机构信息

Department of Liver Surgery, West China Hospital, Sichuan University Medical School, Chengdu, China.

Department of Biochemistry and Molecular Biology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.

出版信息

Cancer Lett. 2023 Apr 10;559:216043. doi: 10.1016/j.canlet.2022.216043. Epub 2022 Dec 27.

Abstract

Immunotherapy plays an increasingly important role in the treatment of most malignant tumors, and CD8 T cells are the most important antitumor effector cells in the process of immunotherapy, and their number and functional status largely determine the antitumor effect. However, under continuous antigen exposure and the stimulation of inflammatory factors, CD8 T cells gradually show a weakened proliferation and effector function, accompanied by the expression of a variety of inhibitory receptors. This state is known as CD8 T cell "exhaustion" and often leads to the loss of control and progression of tumors. Recent studies provided us a better understanding of the mechanisms of T cell exhaustion, this review provides an overview of the activation, exhaustion mechanisms and exhaustion characteristics of CD8 T cells. Although immunotherapy can reverse the exhaustion of CD8 T cells and significantly improve the antitumor effects, single immunotherapy often has limitations, and it is difficult to achieve satisfactory antitumor effects, therefore, this review also summarizes up-to-date information related to cancer immunotherapy, and these emerging insights provide promising clues to the future management of malignant tumors.

摘要

免疫疗法在大多数恶性肿瘤的治疗中起着越来越重要的作用,CD8 T 细胞是免疫治疗过程中最重要的抗肿瘤效应细胞,其数量和功能状态在很大程度上决定了抗肿瘤效果。然而,在持续的抗原暴露和炎症因子的刺激下,CD8 T 细胞逐渐表现出增殖和效应功能减弱,并表达多种抑制性受体。这种状态被称为 CD8 T 细胞“耗竭”,常导致肿瘤失控和进展。最近的研究使我们更好地了解了 T 细胞耗竭的机制,本综述概述了 CD8 T 细胞的激活、耗竭机制和耗竭特征。尽管免疫疗法可以逆转 CD8 T 细胞的耗竭,显著提高抗肿瘤效果,但单一的免疫疗法往往存在局限性,难以达到满意的抗肿瘤效果,因此,本综述还总结了与癌症免疫疗法相关的最新信息,这些新出现的见解为恶性肿瘤的未来管理提供了有希望的线索。

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