Specific Decrease in B-Cell-Derived Extracellular Vesicles Enhances Post-Chemotherapeutic CD8⁺ T Cell Responses

Systemic immunosuppression greatly affects the chemotherapeutic antitumor effect. Here, we showed that CD19⁺ extracellular vesicles (EVs) from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8⁺ T cell responses. Serum CD19⁺ EVs were increased in tumor-bearing mice and patients. Patients with fewer serum CD19⁺ EVs had a better prognosis after chemotherapy. Upregulated hypoxia-inducible factor-1α (HIF-1α) promoted B cells to release CD19⁺ EVs by inducing Rab27a mRNA transcription. Rab27a or HIF-1α deficiency in B cells inhibited CD19⁺ EV production and improved the chemotherapeutic antitumor effect. Silencing of Rab27a in B cells by inactivated Epstein-Barr viruses carrying Rab27a siRNA greatly improved chemotherapeutic efficacy in humanized immunocompromised NOD Prkdc^scidIl2rg^-/- mice. Thus, decreasing CD19⁺ EVs holds high potential to improve the chemotherapeutic antitumor effect.