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Expert Opin Biol Ther. 2011 Sep;11(9):1203-14. doi: 10.1517/14712598.2011.581225. Epub 2011 Jun 26.

Targeting human inducible regulatory T cells (Tr1) in patients with cancer: blocking of adenosine-prostaglandin E₂ cooperation.

Author information

1
University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pathology, 5117 Centre Avenue, Suite 1.27, Pittsburgh, PA 15213, USA. whitesidetl@upmc.edu

Abstract

INTRODUCTION:

Emerging data suggest that human inducible regulatory T cells (Tr1) produce adenosine and prostaglandin E(2) and that these factors cooperate in mediating immune suppression.

AREAS COVERED:

Human Tr1 present in human tumors or blood of cancer patients express ectonucleotidases, CD39 and/or CD73, hydrolyze ATP to adenosine and are COX-2 positive. Expression of CD39 and/or CD73 on human tumors favors expansion and suppressor functions of Tr1. Adenosine and PGE(2) signal via adenosine 2A receptor (A(2A)R) and prostaglandin E(2) receptor 2 (EP(2)R) expressed on effector T (Teff) cells, suppressing their anti-tumor functions by a common mechanism involving upregulation of cytosolic cAMP levels and protein kinase A (PKA) type I activation. The frequency and activity of circulating CD4(+)CD39(+) and CD4(+)COX-2(+) Treg subsets increase in advanced disease and also following oncologic therapies.

EXPERT OPINION:

Pharmacologic blocking of adenosine-PGE(2) collaboration provides a clinically-feasible strategy for disarming of Treg. Used in conjunction with conventional anti-cancer drugs or immune interventions, pharmacologic inhibitors could improve outcome of oncologic therapies.

PMID:
21702720
PMCID:
PMC3149765
DOI:
10.1517/14712598.2011.581225
[Indexed for MEDLINE]
Free PMC Article
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