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Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):11091-6. doi: 10.1073/pnas.1222251110. Epub 2013 Jun 17.

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

Author information

1
Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.

Abstract

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.

KEYWORDS:

ectonucleotidase; immunogenic cell death; immunotherapy

PMID:
23776241
PMCID:
PMC3704029
DOI:
10.1073/pnas.1222251110
[Indexed for MEDLINE]
Free PMC Article

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