CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
英文原题:T-Cell-Derived Extracellular Vesicles with an Antitransferrin Receptor Antibody for Multicancer Targeting.
T-Cell-Derived Extracellular Vesicles with an Antitransferrin Receptor Antibody for Multicancer Targeting.
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近期研究探索了免疫细胞来源的小细胞外囊泡(sEVs)的抗癌特性,但仍存在许多挑战,如需要改善靶向性等。为应对这些挑战,我们工程化改造了携带抗转铁蛋白受体1(TfR1)抗体的T细胞来源sEVs(T-EVs)。通过流式细胞术、免疫细胞化学、活细胞成像和体外阻断实验证实,该修饰增强了sEV对六种癌细胞的递送。T-EVs还降低了PD-L1和Rab27a水平,减少了乳腺癌细胞sEV的产生,并增加了对CD8+ T细胞介导的细胞毒作用的敏感性。全身给药的T-EVs在小鼠模型中有效靶向乳腺、肺和皮肤肿瘤。值得注意的是,T-EVs显著抑制了肿瘤生长,且无全身毒性。此外,T-EVs降低了癌细胞中PD-L1和Rab27a水平,同时增强了CD8+ T细胞的细胞毒性和增殖。总体而言,本研究强调了T-EVs对多种癌症类型的抗癌作用,凸显了其在开发靶向癌症疗法方面的潜力。
Recent research has explored the anticancer properties of immune-cell-derived small extracellular vesicles (sEVs), but many challenges, like the need for improved targeting, remain. To address these challenges, we engineered T-cell-derived sEVs with antitransferrin receptor 1 (TfR1) antibodies (T-EVs).
This modification enhanced the delivery of sEV to six types of cancer cells, as confirmed by flow cytometry, immunocytochemistry, live cell imaging, and blocking experiments in vitro . The T-EVs also reduced PD-L1 and Rab27a levels, decreased sEV production from breast cancer cells, and increased susceptibility to CD8 + T-cell-mediated cytotoxicity. Systemically administered T-EVs efficiently targeted breast, lung, and skin tumors in mouse models.
Notably, T-EVs significantly inhibited tumor growth without systemic toxicity.
Additionally, T-EVs reduced PD-L1 and Rab27a levels in cancer cells while enhancing the CD8 + T-cell cytotoxicity and proliferation.
Overall, this study highlights the anticancer effects of T-EVs against multiple cancer types, underscoring their potential in developing targeted cancer therapies.
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