title: Disarming suppressor cells to improve immunotherapy.
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 E(2) (PGE(2)). Most tumors also express CD39/CD73 and COX-2 and thus contribute to immune suppression. Pharmacologic inhibitors can be used to eliminate adenosine/PGE(2) 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.
authors.affiliation: Departments of Pathology, Immunology and Otolaryngology, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA. whitesidetl@upmc.edu.|Hillman Cancer Center, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA, 15213, USA. whitesidetl@upmc.edu.
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors; D000249:Adenosine Monophosphate / Q000037:antagonists & inhibitors; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D019139:Tumor Escape; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D000249:Adenosine Monophosphate; D015720:5'-Nucleotidase; D015232:Dinoprostone