Abstract
Human tumors can use many different mechanisms to induce dysfunction in the host immune system. Accumulations of inducible regulatory T cells (iTreg, Tr1) are commonly seen in the tumor microenvironment. These Treg express CD39 and up-regulate CD73 ectonucleotidases, hydrolyze exogenous adenosine triphosphate (ATP) to AMP and adenosine and produce prostaglandin E2 (PGE2). Most tumors also express CD39/CD73 and COX-2 and thus contribute to immune suppression. Pharmacologic inhibitors can be used to eliminate adenosine/PGE2 production by Tr1 as well as the tumor or to block binding of these factors to their receptors on Teff or to selectively block cAMP synthesis in Teff. These pharmacologic blocking strategies used alone or in combination with conventional treatments or immunotherapies could disarm Tr1, at the same time restoring antitumor functions of Teff.
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This paper is a Focussed Research Review based on a presentation given at the Second International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2011), held in Budapest, Hungary, May 2–5, 2011. It is part of a CII series of Focussed Research Reviews and meeting report.
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Whiteside, T.L. Disarming suppressor cells to improve immunotherapy. Cancer Immunol Immunother 61, 283–288 (2012). https://doi.org/10.1007/s00262-011-1171-7
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DOI: https://doi.org/10.1007/s00262-011-1171-7