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衰老 T 细胞对癌症免疫治疗的意义

英文原题:Implications of Senescent T Cells for Cancer Immunotherapy.

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Implications of Senescent T Cells for Cancer Immunotherapy.

PubMed 2023/12/14(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

T细胞衰老被认为是由年龄相关的对病原体和肿瘤细胞产生有效应答能力的丧失所导致的。除衰老外,T细胞衰老还可由反复的抗原刺激和慢性炎症引起。此外,我们证明DNA损伤性化疗药物治疗可诱导T细胞衰老。治疗诱导的衰老T(TIS-T)细胞与一般衰老T细胞的特征基本相似。衰老T细胞表现为衰老相关β-半乳糖苷酶阳性群体增加、细胞周期停滞、衰老相关分泌表型因子的分泌以及代谢重编程。此外,衰老T细胞下调共刺激分子CD27和CD28的表达,并上调NK 细胞相关分子。而且,TIS-T细胞显示PD-1表达增加。然而,与T细胞衰老相关的增殖能力丧失和共刺激分子表达减少导致T细胞免疫能力下降。在本综述中,我们讨论衰老T细胞的特征,包括治疗诱导的衰老T细胞。

展开英文摘要原文

T-cell senescence is thought to result from the age-related loss of the ability to mount effective responses to pathogens and tumor cells.

In addition to aging, T-cell senescence is caused by repeated antigenic stimulation and chronic inflammation.

Moreover, we demonstrated that T-cell senescence was induced by treatment with DNA-damaging chemotherapeutic agents. The characteristics of therapy-induced senescent T (TIS-T) cells and general senescent T cells are largely similar. Senescent T cells demonstrate an increase in the senescence-associated beta-galactosidase-positive population, cell cycle arrest, secretion of senescence-associated secretory phenotypic factors, and metabolic reprogramming.

Furthermore, senescent T cells downregulate the expression of the co-stimulatory molecules CD27 and CD28 and upregulate natural killer cell-related molecules.

Moreover, TIS-T cells showed increased PD-1 expression. However, the loss of proliferative capacity and decreased expression of co-stimulatory molecules associated with T-cell senescence cause a decrease in T-cell immunocompetence. In this review, we discuss the characteristics of senescent T-cells, including therapy-induced senescent T cells.

论文信息

作者
Kasamatsu T
单位
Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi 371-8514, Gunma, Japan.Japan
文献类型
综述
期刊
Cancers2023 Dec 14
原文标识
PubMed 38136380 · DOI 10.3390/cancers15245835