The antitumor effect of extracellular vesicles derived from cytokine-activated CD8+ T cells.

IF 3.6 3区医学 Q3 CELL BIOLOGY

Journal of Leukocyte Biology Pub Date : 2024-11-04 DOI:10.1093/jleuko/qiae117

Lin Zhang, Yuan Meng, Yang An, Xuena Yang, Feng Wei, Xiubao Ren

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引用次数: 0

Abstract

Extracellular vesicles (EVs) are nano-sized membrane particles secreted by various cell types that are involved in many important cellular processes. Recently, EVs originating from immune cells, such as dendritic cells, chimeric antigen receptor T cells, and natural killer cells, have attracted much attention because of their known direct and indirect antitumor activity. Here, we report the EVs released by cytokine-activated CD8+ T (caCD8) cells and its cytotoxicity against cancer cells. CaCD8 cells can release EVs following stimulation of CD8+ T cells with an anti-CD3 antibody and a cytokine cocktail ex vivo. The isolated vesicles have typical EV characteristics, such as an oval shape and a size distribution between 30 and 200 nm, as well as CD81 expression. Notably, caCD8-EVs displayed cytotoxicity against various cancer cells in vitro. Furthermore, mechanism analysis demonstrates that caCD8-EVs not only contain typical cytotoxic proteins (i.e. granzyme B and perforin), but also significantly enrich interferon γ (IFNγ) compared with caCD8 cells. EV-derived IFNγ participates in EV-induced apoptosis in cancer cells. Therefore, our data reveal antitumor effects of EVs secreted from caCD8 cells and the potential role of the EV-derived IFNγ.

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细胞因子激活的 CD8+ T 细胞产生的细胞外囊泡的抗肿瘤作用。

细胞外囊泡（EVs）是由各种类型细胞分泌的纳米级膜颗粒，参与了许多重要的细胞过程。最近，源自树突状细胞、嵌合抗原受体 T 细胞（CAR-T）和自然杀伤细胞等免疫细胞的 EVs 因其已知的直接和间接抗肿瘤活性而备受关注。在这里，我们报告了细胞因子激活的 CD8 + T 细胞（caCD8）释放的 EVs 及其对癌细胞的细胞毒性。用抗 CD3 抗体和细胞因子鸡尾酒刺激 CD8+ T 细胞后，CaCD8 细胞可释放 EVs。分离出的囊泡具有典型的EV特征，如椭圆形、大小分布在30-200 nm之间以及CD81表达。值得注意的是，caCD8-EVs 在体外对多种癌细胞具有细胞毒性。此外，机理分析表明，与 caCD8 细胞相比，caCD8-EVs 不仅含有典型的细胞毒性蛋白（即颗粒酶 B 和穿孔素），还显著富集了 IFNγ。源自 EVs 的 IFNγ 参与了 EVs 诱导的癌细胞凋亡。因此，我们的数据揭示了 caCD8 细胞分泌的 EVs 的抗肿瘤作用以及 EVs 衍生的 IFNγ 的潜在作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Leukocyte Biology 医学-免疫学

CiteScore

11.50

自引率

0.00%

发文量

358

审稿时长

2 months

期刊介绍： JLB is a peer-reviewed, academic journal published by the Society for Leukocyte Biology for its members and the community of immunobiologists. The journal publishes papers devoted to the exploration of the cellular and molecular biology of granulocytes, mononuclear phagocytes, lymphocytes, NK cells, and other cells involved in host physiology and defense/resistance against disease. Since all cells in the body can directly or indirectly contribute to the maintenance of the integrity of the organism and restoration of homeostasis through repair, JLB also considers articles involving epithelial, endothelial, fibroblastic, neural, and other somatic cell types participating in host defense. Studies covering pathophysiology, cell development, differentiation and trafficking; fundamental, translational and clinical immunology, inflammation, extracellular mediators and effector molecules; receptors, signal transduction and genes are considered relevant. Research articles and reviews that provide a novel understanding in any of these fields are given priority as well as technical advances related to leukocyte research methods.