Impaired Th1 immunity in ovarian cancer patients is mediated by TNFR2+ Tregs within the tumor microenvironment.
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.
Department of Immunology, Monash University, Alfred Medical and Research Precinct, Prahran, VIC 3181, Australia. Electronic address: chindu.govindaraj@monash.edu.
Chindu
C
Govindaraj
Karen
K
Scalzo-Inguanti
Mutsa
M
Madondo
Julene
J
Hallo
Katie
K
Flanagan
Michael
M
Quinn
Magdalena
M
Plebanski
D015720:5'-Nucleotidase / Q000276:immunology; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D001081:Apyrase / Q000276:immunology; D001201:Ascites / Q000276:immunology; D060908:CTLA-4 Antigen / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology*
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D058851:GPI-Linked Proteins; C087215:LRRC32 protein, human; D008565:Membrane Proteins; D047889:Receptors, Tumor Necrosis Factor, Type II; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D001081:Apyrase; C067869:CD39 antigen
Ascites;; Immune suppression; Ovarian cancer;; Regulatory T cells;; TNF receptor 2;