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Clin Immunol. 2013 Oct;149(1):97-110. doi: 10.1016/j.clim.2013.07.003. Epub 2013 Jul 25.

Impaired Th1 immunity in ovarian cancer patients is mediated by TNFR2+ Tregs within the tumor microenvironment.

Author information

1
Department of Immunology, Monash University, Alfred Medical and Research Precinct, Prahran, VIC 3181, Australia. Electronic address: chindu.govindaraj@monash.edu.

Abstract

Ovarian cancer is a prevalent gynecological malignancy with potent immune-suppression capabilities; regulatory T cells (Tregs) are significant contributors to this immune-suppression. As ovarian cancer patients present with high levels of TNF and Tregs expressing TNFR2 are associated with maximal suppressive capacity, we investigated TNFR2+ Tregs within these patients. Indeed, TNFR2+ Tregs from tumor-associated ascites were the most potent suppressor T cell fraction. They were abundantly present within the ascites and more suppressive than peripheral blood TNFR2+ Tregs in patients. The increased suppressive capacity can be explained by a distinct cell surface expression profile, which includes high levels of CD39, CD73, TGF-β and GARP. Additionally, CD73 expression level on TNFR2+ Tregs was inversely correlated with IFN-γ production by effector T cells. This Treg fraction can be selectively recruited into the ascites from the peripheral blood of patients. Targeting TNFR2+ Tregs may offer new approaches to enhance the poor survival rates of ovarian cancer.

KEYWORDS:

Ascites;; Immune suppression; Ovarian cancer;; Regulatory T cells;; TNF receptor 2;

PMID:
23948613
DOI:
10.1016/j.clim.2013.07.003
[Indexed for MEDLINE]

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