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- W2316376858 abstract "It is increasingly being recognised that the tumor microenvironment modulates the effector functions of tumor-infiltrating lymphocytes and consequently suppresses anti-tumor immunity. One immunosuppressive component of the tumor microenvironment is elevated levels of adenosine. The conversion of ATP into adenosine occurs in a stepwise manner essentially through the enzymatic activity of CD39 (NTPDase I) (ATP>AMP) and CD73 (ecto-5′-nucleotidase- AMP>adenosine). CD73 is a glycosylphosphatidyl-inositol (GPI)-linked cell surface enzyme constitutively expressed on endothelial cells, foxp3+ Tregs and subsets of leukocytes, and is considered as the rate-limiting enzyme in the production of extracellular adenosine. We have recently demonstrated that one of the mechanisms contributing to the immunosuppressive accumulation of extracellular adenosine in tumors is the expression of CD73 by tumor cells, but CD73 expression on foxp3+ Tregs is also important for their suppression of anti-tumor immunity. We now report on the role of host-derived CD73 in de novo tumor development in mice. Combinations of anti-CD73 with agonist and T cell checkpoint blockade antibodies demonstrate significant beneficial effects in experimental and de novo models of tumorigenesis. In humans using large cohorts we have shown that CD73 is highest in triple negative breast cancer (TNBC) and expression correlates with an invasion marker and the lack of ER signalling. CD73 expression is also associated with a worse prognosis in TNBC irrespective of treatment and predicts response to anthracycline therapy. The development of CD73 as a target for cancer immunotherapy will be further discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5408. doi:1538-7445.AM2012-5408" @default.
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- W2316376858 date "2012-04-15" @default.
- W2316376858 modified "2023-09-25" @default.
- W2316376858 title "Abstract 5408: CD73 as a target in cancer immunotherapy" @default.
- W2316376858 doi "https://doi.org/10.1158/1538-7445.am2012-5408" @default.
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