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Expert Opin Biol Ther. 2012 Oct;12(10):1383-97. doi: 10.1517/14712598.2012.707184. Epub 2012 Jul 31.

Induced and natural regulatory T cells in human cancer.

Author information

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

Abstract

INTRODUCTION:

Evidence suggests that FOXP3(+)CD25(high)CD4(+) regulatory T cells (Treg) which accumulate in cancer may have beneficial or unfavorable effects on prognosis. The presence in tumor-associated inflammatory infiltrates of two subsets of Treg with distinct phenotypic and functional profiles might explain these conflicting observations.

AREAS COVERED:

Human inducible (i) Treg arising by tumor-driven conversion of conventional CD4(+) T cells are highly suppressive, therapy-resistant Treg which down-regulate anti-tumor immune responses, promoting tumor growth. Natural (n) Treg, normally responsible for maintaining peripheral tolerance, control cancer-associated inflammation, which favors tumor progression. This division of labor between nTreg and iTreg is not absolute, and overlap may be common. Nevertheless, iTreg play a critical and major role in cancer and cancer therapy. The tumor microenvironment determines the type, frequency and suppression levels of accumulating Treg.

EXPERT OPINION:

In cancer, a selective removal or silencing of iTreg and not of nTreg should be a therapeutic goal. However, the implementation of this challenging strategy requires further studies of cellular and molecular crosstalk among immune cells in the tumor microenvironment.

PMID:
22849383
PMCID:
PMC3730844
DOI:
10.1517/14712598.2012.707184
[Indexed for MEDLINE]
Free PMC Article

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