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

被引：157

作者：

Zhang, Fanghui ^{[1
,2
,3
,4
,5
,6
]}

Li, Rongrong ^{[1
,2
]}

Yang, Yunshan ^{[7
]}

Shi, Chunhui ^{[8
]}

Shen, Yingying ^{[1
,2
]}

Lu, Chaojie ^{[1
,2
]}

Chen, Yinghu ^{[9
]}

Zhou, Wu ^{[10
]}

Lin, Aifu ^{[11
]}

Yu, Lei ^{[12
]}

Zhang, Wanjing ^{[1
,2
]}

Xue, Zhenwei ^{[1
,2
]}

Wang, Jianli ^{[3
,4
,5
,6
]}

Cai, Zhijian ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Inst Immunol, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China

[2] Zhejiang Univ, Dept Orthopaed, Affiliated Hosp 2, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China

[3] Zhejiang Univ, Inst Immunol, Sch Med, Affiliated Hosp 1, Hangzhou 310058, Zhejiang, Peoples R China

[4] Zhejiang Univ, Bone Marrow Transplantat Ctr, Sch Med, Affiliated Hosp 1, Hangzhou 310058, Zhejiang, Peoples R China

[5] Zhejiang Univ, Inst Hematol, Hangzhou 310006, Zhejiang, Peoples R China

[6] Zhejiang Engn Lab Stem Cell & Immunotherapy, Hangzhou 310006, Zhejiang, Peoples R China

[7] Zhejiang Canc Hosp, Dept Chemotherapy, Hangzhou 310022, Zhejiang, Peoples R China

[8] Yuhuan Hosp Tradit Chinese Med, Dept Gynaecol & Obstet, Taizhou 317600, Peoples R China

[9] Zhejiang Univ, Childrens Hosp, Div Infect Dis, Zhejiang Key Lab Neonatal Dis,Sch Med, Hangzhou 310006, Zhejiang, Peoples R China

[10] Lishui Univ, Coll Med & Hlth, Dept Med, Lishui 323000, Peoples R China

[11] Zhejiang Univ, Coll Life Sci, Hangzhou 310058, Zhejiang, Peoples R China

[12] Zhejiang Univ, Sir Run Run Shaw Hosp, Lab Canc Biol, Key Lab Biotherapy Zhejiang,Med Sch, Hangzhou 310020, Zhejiang, Peoples R China

来源：

IMMUNITY | 2019年 / 50卷 / 03期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

ADENOSINE; CANCER; CD73; LYMPHOCYTES; GENERATION; PROTECTS; EXOSOMES; CD39;

D O I：

10.1016/j.immuni.2019.01.010

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：738 / +

页数：20

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