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.
我们的工作确立了CD81作为连接放射抵抗与免疫逃逸的关键桥梁,其通过维持GBM中CD274的丰度发挥作用,并突显CD81作为优化放射免疫治疗的有前景的治疗靶点。
英文原题:Tumor vaccine based on extracellular vesicles derived from γδ-T cells exerts dual antitumor activities.
本研究为使用同种异体γδ-T-EVs疫苗在癌症控制中提供了概念验证。
γδ-T 细胞是兼具双重抗肿瘤活性的固有样 T 细胞。它们既能直接清除肿瘤细胞,又能作为免疫刺激细胞促进抗肿瘤免疫。既往研究已证明,来源于 γδ-T 细胞的小细胞外囊泡(EVs)(γδ-T-EVs)继承了其亲本细胞的双重抗肿瘤活性。然而,γδ-T-EVs 能否被设计为肿瘤疫苗以提高治疗效果仍不清楚。本研究发现,γδ-T-EVs 对抗原呈递细胞具有免疫佐剂效应,表现为 γδ-T-EVs 处理后 DCs 的抗原呈递分子和共刺激分子表达增强、促炎细胞因子分泌增加以及抗原呈递能力增强。基于 γδ-T-EVs 的疫苗是通过将肿瘤相关抗原(TAAs)装载到 γδ-T-EVs 中设计的。与 γδ-T-EVs 相比,基于 γδ-T-EVs 的疫苗有效促进了更多肿瘤特异性 T 细胞应答。此外,该疫苗方案保留了直接抗肿瘤效应并诱导肿瘤细胞凋亡。有趣的是,同种异体基于 γδ-T-EVs 的疫苗显示出与自体对应物相当的预防性和治疗性抗肿瘤效果,表明其在临床实践中具有更好的集中化和标准化途径。此外,同种异体基于 γδ-T-EVs 的疫苗通过其双重抗肿瘤活性显示出优于基于 DC-EVs 的疫苗。本研究为使用同种异体基于 γδ-T-EVs 的疫苗进行肿瘤控制提供了概念验证。
γδ-T cells are innate-like T cells with dual antitumor activities. They can directly eradicate tumor cells and function as immunostimulatory cells to promote antitumor immunity. Previous studies have demonstrated that small extracellular vesicles (EVs) derived from γδ-T cells (γδ-T-EVs) inherited the dual antitumor activities from their parental cells. However, it remains unknown whether γδ-T-EVs can be designed as tumors vaccine to improve therapeutic efficacy. Here, we found that γδ-T-EVs had immune adjuvant effects on antigen-presenting cells, as revealed by enhanced expression of antigen-presenting and co-stimulatory molecules, secretion of pro-inflammatory cytokines and antigen-presenting ability of DCs after γδ-T-EVs treatment. The γδ-T-EVs-based vaccine was designed by loading tumor-associated antigens (TAAs) into γδ-T-EVs. Compared with γδ-T-EVs, the γδ-T-EVs-based vaccine effectively promoted more tumor-specific T-cell responses. In addition, the vaccine regimen preserved direct antitumor effects and induced tumor cell apoptosis. Interestingly, the allogeneic γδ-T-EVs-based vaccine showed comparable preventive and therapeutic antitumor effects to their autologous counterparts, indicating a better way of centralization and standardization in clinical practice. Furthermore, the allogeneic γδ-T-EVs-based vaccine displayed advantages over the DC-EVs-based vaccine through their dual antitumor activities. This study provides a proof-of-concept for using the allogeneic γδ-T-EVs-based vaccine in cancer control.
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