文章：

衰老T细胞对癌症免疫治疗的影响

Implications of Senescent T Cells for Cancer Immunotherapy

原文发布日期：14 December 2023

DOI: 10.3390/cancers15245835

类型: Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

T细胞衰老被认为源于随年龄增长而丧失对病原体和肿瘤细胞产生有效反应的能力。除衰老外，T细胞衰老还由反复抗原刺激和慢性炎症引起。此外，我们证实DNA损伤性化疗药物处理亦可诱导T细胞衰老。治疗诱导衰老T细胞（TIS-T）与普通衰老T细胞的特征高度相似：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分泌及代谢重编程。同时，衰老T细胞下调共刺激分子CD27和CD28表达，上调自然杀伤细胞相关分子。值得注意的是，TIS-T细胞还表现出PD-1表达增强。然而，伴随T细胞衰老出现的增殖能力丧失与共刺激分子表达降低，最终导致T细胞免疫应答能力下降。本综述系统探讨了衰老T细胞（包括治疗诱导衰老T细胞）的特征表现。

原文链接：

Implications of Senescent T Cells for Cancer Immunotherapy