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T 细胞衰老:肺癌免疫治疗的新视角。

T cell senescence: a new perspective on immunotherapy in lung cancer.

机构信息

College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.

College of Traditional Chinese Medicine, Weifang Medical University, Weifang, China.

出版信息

Front Immunol. 2024 Feb 13;15:1338680. doi: 10.3389/fimmu.2024.1338680. eCollection 2024.

Abstract

T cell senescence is an indication of T cell dysfunction. The ability of senescent T cells to respond to cognate antigens is reduced and they are in the late stage of differentiation and proliferation; therefore, they cannot recognize and eliminate tumor cells in a timely and effective manner, leading to the formation of the suppressive tumor microenvironment. Establishing methods to reverse T cell senescence is particularly important for immunotherapy. Aging exacerbates profound changes in the immune system, leading to increased susceptibility to chronic, infectious, and autoimmune diseases. Patients with malignant lung tumors have impaired immune function with a high risk of recurrence, metastasis, and mortality. Immunotherapy based on PD-1, PD-L1, CTLA-4, and other immune checkpoints is promising for treating lung malignancies. However, T cell senescence can lead to low efficacy or unsuccessful treatment results in some immunotherapies. Efficiently blocking and reversing T cell senescence is a key goal of the enhancement of tumor immunotherapy. This study discusses the characteristics, mechanism, and expression of T cell senescence in malignant lung tumors and the treatment strategies.

摘要

T 细胞衰老表明 T 细胞功能障碍。衰老 T 细胞对同源抗原的反应能力降低,且处于分化和增殖的晚期;因此,它们无法及时有效地识别和清除肿瘤细胞,导致抑制性肿瘤微环境的形成。建立逆转 T 细胞衰老的方法对于免疫治疗尤为重要。衰老会加剧免疫系统的深刻变化,导致慢性、感染性和自身免疫性疾病的易感性增加。患有恶性肺肿瘤的患者免疫功能受损,复发、转移和死亡的风险较高。基于 PD-1、PD-L1、CTLA-4 和其他免疫检查点的免疫疗法有望治疗肺癌。然而,T 细胞衰老会导致一些免疫疗法的疗效降低或治疗失败。有效阻断和逆转 T 细胞衰老,是增强肿瘤免疫治疗的关键目标。本研究讨论了恶性肺肿瘤中 T 细胞衰老的特征、机制和表达,以及治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc9c/10896971/418dad6b8617/fimmu-15-1338680-g001.jpg

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