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

Chindu Govindaraj, Karen Scalzo-Inguanti, Mutsa Madondo, Julene Halo, Katie L Flanagan, Michael Quinn, Magdalena Plebanski

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72 Citations (Scopus)

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-? and GARP. Additionally, CD73 expression level on TNFR2. + Tregs was inversely correlated with IFN-? 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. ? 2013 Elsevier Inc.
Original languageEnglish
Pages (from-to)97 - 110
Number of pages14
JournalClinical Immunology
Volume149
Issue number1
DOIs
Publication statusPublished - 2013

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