Electronic Resource

CD73 promotes resistance to HER2/ErbB2 antibody therapy

Bibliographic Details
Title: CD73 promotes resistance to HER2/ErbB2 antibody therapy
Source: Cancer research, 77 (20
Publisher Information: 2017-10
Added Details: Turcotte, Martin
Joensuu, Heikki
Kellokumpu-Lehtinen, Pirkko-Liisa
Sotiriou, Christos
Smyth, Mark John
Stagg, John
Allard, David
Mittal, Deepak
Bareche, Yacine
Buisseret, Laurence
Jose, Vinu
Pommey, Sandra
Delisle, Vincent
Loi, Sherene
Document Type: Electronic Resource
Abstract: Expression of the ectonucleotidase CD73 by tumor cells, stromal cells, and immune cells is associated in cancer with immune suppression. In this study, we investigated the role of CD73 on the activity of the anti-HER2/ErbB2 monoclonal antibody (mAb) trastuzumab. In a prospective, randomized phase III clinical trial evaluating the activity of trastuzumab, high levels of CD73 gene expression were associated significantly with poor clinical outcome. In contrast, high levels of PD-1 and PD-L1 were associated with improved clinical outcome. In immunocompetent mouse models of HER2/ErbB2–driven breast cancer, CD73 expression by tumor cells and host cells significantly suppressed immune-mediated responses mediated by anti-ErbB2 mAb. Furthermore, anti-CD73 mAb therapy enhanced the activity of anti-ErbB2 mAb to treat engrafted or spontaneous tumors as well as lung metastases. Gene ontology enrichment analysis from gene-expression data revealed a positive association of CD73 expression with extracellular matrix organization, TGFb genes, epithelial-to-mesenchymal transition (EMT) transcription factors and hypoxia-inducible-factor (HIF)-1 gene signature. Human mammary cells treated with TGFb or undergoing EMT upregulated CD73 cell-surface expression, confirming roles for these pathways. In conclusion, our findings establish CD73 in mediating resistance to trastuzumab and provide new insights into how CD73 is regulated in breast cancer.
SCOPUS: ar.j
Index Terms: Cancérologie, 5'-Nucleotidase -- immunology, Animals, Antibodies, Monoclonal -- immunology -- physiology, Antigens, CD -- immunology, Antigens, Neoplasm -- immunology, Breast Neoplasms -- immunology -- pathology -- therapy, Cell Line, Tumor, Disease Models, Animal, Drug Resistance, Neoplasm, Female, GPI-Linked Proteins -- immunology, Humans, Mice, Mice, Inbred BALB C, Mice, Transgenic, Molecular Targeted Therapy, Random Allocation, Receptor, ErbB-2 -- immunology, Signal Transduction, Tetraspanins -- immunology, Trastuzumab -- immunology -- pharmacology, info:eu-repo/semantics/article, info:ulb-repo/semantics/articlePeerReview, info:ulb-repo/semantics/openurl/article
URL: https://dipot.ulb.ac.be/dspace/bitstream/2013/260723/1/doi_244350.pdf
Availability: Open access content. Open access content
1 full-text file(s): info:eu-repo/semantics/restrictedAccess
Note: 1 full-text file(s): application/pdf
Other Numbers: EQY oai:dipot.ulb.ac.be:2013/260723
From OAIster®, provided by the OCLC Cooperative.
Accession Number: edsoai.on1014239642
Database: OAIster
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