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Publication

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

Immunity | 2019

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 PrkdcscidIl2rg-/- mice. Thus, decreasing CD19+ EVs holds high potential to improve the chemotherapeutic antitumor effect.

Pubmed ID: 30770248 RIS Download

Research resources used in this publication

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Additional research tools detected in this publication

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Antibodies used in this publication

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Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

PE anti-mouse CD9 (antibody)

RRID:AB_1279325

This monoclonal targets CD9

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Mouse Anti-Human CD63 (MX-49.129.5) Monoclonal, Unconjugated, Clone Mx-49.129.5 (antibody)

RRID:AB_627877

This monoclonal targets Human CD63

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CD39 antibody [EPR3678(2)] (antibody)

RRID:AB_10890104

This monoclonal targets CD39 antibody [EPR3678(2)]

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CD19 Monoclonal Antibody (HIB19), Biotin, eBioscience (antibody)

RRID:AB_466388

This monoclonal targets CD19

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HIF1A-human (antibody)

RRID:AB_10001154

This monoclonal targets HIF1A

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Alix antibody (antibody)

RRID:AB_2162467

This polyclonal targets Alix

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CD19 Monoclonal Antibody (MB19-1), Biotin, eBioscience (antibody)

RRID:AB_466384

This monoclonal targets CD19

View all literature mentions

GM130 antibody [EP892Y] (antibody)

RRID:AB_880266

This monoclonal targets GM130 antibody [EP892Y]

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GRP94 antibody - ER Marker (antibody)

RRID:AB_303992

This polyclonal targets GRP94 antibody - ER Marker

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Mouse Anti-Hsp70 Monoclonal Antibody, Unconjugated, Clone 7 (antibody)

RRID:AB_397942

This monoclonal targets Hsp70

View all literature mentions

anti-mouse CD4 (antibody)

RRID:AB_1107636

This monoclonal targets CD4

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InVivoMab anti-mouse CD73 (antibody)

RRID:AB_10950310

This monoclonal targets CD73

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InVivoPlus anti-mouse CD8α (antibody)

RRID:AB_1107671

This monoclonal targets CD8α

View all literature mentions

CD4 Monoclonal Antibody (SK3 (SK-3)), PE, eBioscience (antibody)

RRID:AB_1518751

This monoclonal targets CD4

View all literature mentions

Alexa Fluor(R) 594 anti-human CD8a (antibody)

RRID:AB_2563232

This monoclonal targets CD8a

View all literature mentions

PE anti-human CD19 (antibody)

RRID:AB_314237

This monoclonal targets CD19

View all literature mentions

CD3e Monoclonal Antibody (145-2C11), Biotin, eBioscience (antibody)

RRID:AB_466319

This monoclonal targets CD3e

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APC anti-human CD45 (antibody)

RRID:AB_314399

This monoclonal targets CD45

View all literature mentions

PE anti-human CD9 (antibody)

RRID:AB_2075892

This monoclonal targets CD9

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FITC anti-mouse CD8a (antibody)

RRID:AB_312744

This monoclonal targets CD8a

View all literature mentions

IFN gamma Monoclonal Antibody (XMG1.2), PE, eBioscience (antibody)

RRID:AB_466193

This monoclonal targets IFN gamma

View all literature mentions

APC anti-mouse CD8a (antibody)

RRID:AB_312750

This monoclonal targets CD8a

View all literature mentions

Pacific Blue(TM) anti-mouse CD45 (antibody)

RRID:AB_493535

This monoclonal targets CD45

View all literature mentions

Granzyme B Monoclonal Antibody (NGZB), PE, eBioscience (antibody)

RRID:AB_10870787

This monoclonal targets Granzyme B

View all literature mentions

PE anti-mouse/human CD45R/B220 (antibody)

RRID:AB_312992

This monoclonal targets CD45R

View all literature mentions

CD39 Monoclonal Antibody (24DMS1), PE, eBioscience (antibody)

RRID:AB_1210740

This monoclonal targets CD39

View all literature mentions

CD45R (B220) Monoclonal Antibody (RA3-6B2), Alexa Fluor™ 488, eBioscience (antibody)

RRID:AB_469907

This monoclonal targets CD45R (B220)

View all literature mentions

APC anti-mouse CD19 (antibody)

RRID:AB_2629838

This monoclonal targets CD19

View all literature mentions

APC anti-mouse CD3 (antibody)

RRID:AB_2561455

This monoclonal targets CD3

View all literature mentions

CD73 Monoclonal Antibody (eBioTY/11.8 (TY/11.8)), PE, eBioscience (antibody)

RRID:AB_763513

This monoclonal targets CD73

View all literature mentions

IgD Monoclonal Antibody (11-26c (11-26)), PE, eBioscience (antibody)

RRID:AB_466113

This monoclonal targets IgD

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CD23 Monoclonal Antibody (B3B4), PE-Cyanine7, eBioscience (antibody)

RRID:AB_469604

This monoclonal targets CD23

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IgM Monoclonal Antibody (II/41), APC-eFluor™ 780, eBioscience (antibody)

RRID:AB_2573984

This monoclonal targets IgM

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CD21/CD35 Monoclonal Antibody (eBio4E3 (4E3)), FITC, eBioscience (antibody)

RRID:AB_464976

This monoclonal targets CD21/CD35

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CD43 Monoclonal Antibody (eBioR2/60), PE, eBioscience (antibody)

RRID:AB_465659

This monoclonal targets CD43

View all literature mentions

Rab 5B (F-9) (antibody)

RRID:AB_10917429

This monoclonal targets Rab 5B (F-9)

View all literature mentions

CD45R (B220) Monoclonal Antibody (RA3-6B2), APC, eBioscience (antibody)

RRID:AB_469395

This monoclonal targets CD45R (B220)

View all literature mentions

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