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-1 alpha (HIF-1 alpha) promoted B cells to release CD19(+) EVs by inducing Rab27a mRNA transcription. Rab27a or HIF-1 alpha 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(scid) Il2rg(-/-) mice. Thus, decreasing CD19(+) EVs holds high potential to improve the chemotherapeutic antitumor effect.