CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer

被引：406

作者：

Loi, Sherene ^{[1
]}

Pommey, Sandra ^{[2
,3
]}

Haibe-Kains, Benjamin ^{[4
]}

Beavis, Paul A. ^{[5
]}

Darcy, Phillip K. ^{[5
,6
]}

Smyth, Mark J. ^{[5
,6
,7
,8
]}

Stagg, John ^{[2
,3
]}

机构：

[1] Peter MacCallum Canc Ctr, Div Canc Med & Res, East Melbourne, Vic 3002, Australia

[2] Ctr Hosp Univ Montreal, Fac Pharm, Ctr Rech, Montreal, PQ H2L 4M1, Canada

[3] Ctr Hosp Univ Montreal, Inst Canc Montreal, Ctr Rech, Montreal, PQ H2L 4M1, Canada

[4] Inst Rech Clin Montreal, Bioinformat & Computat Genom Lab, Montreal, PQ H2W 1R7, Canada

[5] Peter MacCallum Canc Ctr, Canc Immunol Program, Trescowthick Labs, East Melbourne, Vic 3002, Australia

[6] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3010, Australia

[7] Queensland Inst Med Res, Immmunol Canc & Infect Lab, Herston, Qld 4006, Australia

[8] Univ Queensland, Sch Med, Herston, Qld 4006, Australia

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 27期

基金：

英国医学研究理事会; 加拿大健康研究院;

关键词：

ectonucleotidase; immunogenic cell death; immunotherapy; ESTROGEN-RECEPTOR; TUMOR-GROWTH; ADENOSINE; THERAPY; ECTO-5'-NUCLEOTIDASE; HETEROGENEITY; CHEMOTHERAPY; CELLS;

D O I：

10.1073/pnas.1222251110

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Using gene-expression data from over 6,000 breast cancer patients, we report herein that high CD73 expression is associated with a poor prognosis in triple-negative breast cancers (TNBC). Because anthracycline-based chemotherapy regimens are standard treatment for TNBC, we investigated the relationship between CD73 and anthracycline efficacy. In TNBC patients treated with anthracycline-only preoperative chemotherapy, high CD73 gene expression was significantly associated with a lower rate of pathological complete response or the disappearance of invasive tumor at surgery. Using mouse models of breast cancer, we demonstrated that CD73 overexpression in tumor cells conferred chemoresistance to doxorubicin, a commonly used anthracycline, by suppressing adaptive antitumor immune responses via activation of A2A adenosine receptors. Targeted blockade of CD73 enhanced doxorubicin-mediated antitumor immune responses and significantly prolonged the survival of mice with established metastatic breast cancer. Taken together, our data suggest that CD73 constitutes a therapeutic target in TNBC.

引用

页码：11091 / 11096

页数：6

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