γδ-T细胞是具有双重抗肿瘤活性的先天类T细胞。它们可以直接清除肿瘤细胞，并作为免疫刺激细胞促进抗肿瘤免疫。以前的研究表明，来源于γδ-T细胞的小型胞外囊泡（EVs）（γδ-T-EVs）从其母细胞中继承了双重抗肿瘤活性。然而，尚不清楚γδ-T-EVs是否可以被设计为肿瘤疫苗以提高治疗效果。在这里，我们发现γδ-T-EVs对抗原递呈细胞具有免疫佐剂效应，表现为增强抗原递呈和共刺激分子的表达，促炎细胞因子的分泌以及经γδ-T-EVs治疗后DCs的抗原递呈能力。γδ-T-EVs基于疫苗通过将肿瘤相关抗原（TAAs）装载到γδ-T-EVs中。与γδ-T-EVs相比，γδ-T-EVs基于疫苗有效促进了更多的肿瘤特异性T细胞反应。此外，疫苗方案保留了直接的抗肿瘤效应并诱导了肿瘤细胞凋亡。有趣的是，异基因γδ-T-EVs基于疫苗与其同基因对应物一样在预防和治疗抗肿瘤效应方面表现出可比性，这表明了在临床实践中的更好的集中和标准化途径。此外，与DC-EVs基于疫苗相比，异基因γδ-T-EVs基于疫苗通过其双重抗肿瘤活性显示出优势。本研究为在癌症控制中使用异基因γδ-T-EVs基于疫苗提供了概念验证。© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

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.© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.