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

Loi, Sherene, Pommey, Sandra, Haibe-Kains, Benjamin, Beavis, Paul A., Darcy, Phillip K., Smyth, Mark J. and Stagg, John (2013) CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer. Proceedings of the National Academy of Sciences of the United States of America, 110 27: 11091-11096. doi:10.1073/pnas.1222251110


Author Loi, Sherene
Pommey, Sandra
Haibe-Kains, Benjamin
Beavis, Paul A.
Darcy, Phillip K.
Smyth, Mark J.
Stagg, John
Title CD73 promotes anthracycline resistance and poor prognosis in triple negative breast cancer
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 0027-8424
1091-6490
Publication date 2013-07
Sub-type Article (original research)
DOI 10.1073/pnas.1222251110
Open Access Status
Volume 110
Issue 27
Start page 11091
End page 11096
Total pages 6
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Collection year 2014
Language eng
Abstract Using gene-expression data from over 6,000 breast cancer patients, wereport 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.
Keyword Ectonucleotidase
Immunogenic cell death
Immunotherapy
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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