CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
细胞因子激活的 CD8+ T 细胞来源的细胞外囊泡的抗肿瘤作用
英文原题：The antitumor effect of extracellular vesicles derived from cytokine-activated CD8+ T cells.
查看英文原题
The antitumor effect of extracellular vesicles derived from cytokine-activated CD8+ T cells.
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中文摘要
细胞外囊泡（EVs）是由多种细胞类型分泌的纳米级膜颗粒，参与许多重要的细胞过程。近年来，来源于免疫细胞的EVs，如树突状细胞、CAR-T 细胞和NK 细胞，因其已知的直接和间接抗肿瘤活性而备受关注。
在此，我们报道了由细胞因子激活的CD8+ T（caCD8）细胞释放的EVs及其对癌细胞的细胞毒性。caCD8细胞在体外经抗CD3抗体和细胞因子混合物刺激CD8+ T细胞后能够释放EVs。分离得到的囊泡具有典型的EV特征，如椭圆形形态、30至200 nm的粒径分布以及CD81表达。
值得注意的是，caCD8-EVs在体外对多种癌细胞表现出细胞毒性。此外，机制分析表明，caCD8-EVs不仅含有典型的细胞毒性蛋白（即颗粒酶B和穿孔素），而且与caCD8细胞相比显著富集干扰素γ（IFNγ）。EV来源的IFNγ参与了EV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的抗肿瘤效应以及EV来源IFNγ的潜在作用。
展开英文摘要原文
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.
论文信息
- 作者
- Zhang L、Meng Y、An Y、Yang X、Wei F、Ren X
- 单位
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin 300060, China.China
- 期刊
- Journal of leukocyte biology2024 Nov 4
- 原文标识
- PubMed 38753658 · DOI 10.1093/jleuko/qiae117
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