Tumor vaccine based on extracellular vesicles derived from ?d-T cells exerts dual antitumor activities

?d-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 ?d-T cells (?d-T-EVs) inherited the dual antitumor activities from their parental cells. However, it remains unknown whether ?d-T-EVs can be designed as tumors vaccine to improve therapeutic efficacy. Here, we found that ?d-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 ?d-T-EVs treatment. The ?d-T-EVs-based vaccine was designed by loading tumor-associated antigens (TAAs) into ?d-T-EVs. Compared with ?d-T-EVs, the ?d-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 ?d-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 ?d-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 ?d-T-EVs-based vaccine in cancer control.