| First Author | Zhang F | Year | 2019 |
| Journal | Immunity | Volume | 50 |
| Issue | 3 | Pages | 738-750.e7 |
| PubMed ID | 30770248 | Mgi Jnum | J:305807 |
| Mgi Id | MGI:6706535 | Doi | 10.1016/j.immuni.2019.01.010 |
| Citation | Zhang F, et al. (2019) Specific Decrease in B-Cell-Derived Extracellular Vesicles Enhances Post-Chemotherapeutic CD8(+) T Cell Responses. Immunity 50(3):738-750.e7 |
| abstractText | 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-1alpha (HIF-1alpha) promoted B cells to release CD19(+) EVs by inducing Rab27a mRNA transcription. Rab27a or HIF-1alpha 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. |
