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

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


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;.

MeSH terms

  • 5'-Nucleotidase / immunology
  • Aged
  • Antigens, CD / immunology
  • Apyrase / immunology
  • Ascites / immunology
  • CTLA-4 Antigen / immunology
  • Cytokines / immunology
  • Female
  • Forkhead Transcription Factors / immunology
  • GPI-Linked Proteins / immunology
  • Humans
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Membrane Proteins / immunology
  • Middle Aged
  • Ovarian Neoplasms / immunology*
  • Receptors, Tumor Necrosis Factor, Type II / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Microenvironment / immunology*


  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • GPI-Linked Proteins
  • LRRC32 protein, human
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor, Type II
  • 5'-Nucleotidase
  • NT5E protein, human
  • Apyrase
  • CD39 antigen