The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer.
OBJECTIVE
The forkhead box transcription factor FoxP3 is specifically expressed in T cells with regulatory properties (Treg). Recently, high numbers of Treg were described to be associated with poor survival in different malignancies. The aim of the presented study was determine the prognostic effect of FoxP3 mRNA expression (reflecting the tissue content of Treg) in ovarian carcinoma and its relation with cytokines, such as IFN-gamma.


METHODS
Total RNA was isolated from 99 ovarian carcinoma and from 14 healthy ovarian biopsies. Real-time PCR for FoxP3 was done and correlated with IFN-gamma-, CD3-, IRF-1-, SOCS-1-, HER-2-, and iNOS expression as well as patients' outcome. The mRNA data was corroborated by FoxP3 immunohistochemistry.


RESULTS
Quantitation of FoxP3 expression identified a patient subgroup (>81th percentile), which is characterized by a significantly worse prognosis in terms of overall survival (27.8 versus 77.3 months, P = 0.0034) and progression-free survival (18 versus 57.5 months; P = 0.0041). FoxP3 expression correlated with IFN-gamma, IRF-1, and CD3 expression. High FoxP3 expression represents an independent prognostic factor for overall survival (P = 0.004) and progression-free survival (P = 0.004).


CONCLUSIONS
High expression levels of FoxP3 might represent a surrogate marker for an immunosuppressive milieu contributing to tumor immune escape. Strategies selectively depleting Treg might improve the antitumor activity of endogenously arising tumor-reactive T cells and immunotherapies using vaccines or antibodies.
Wolf
Dominik
D
Division of Hematology and Oncology, Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria.
Wolf
Anna M
AM
Rumpold
Holger
H
Fiegl
Heidi
H
Zeimet
Alain G
AG
Muller-Holzner
Elisabeth
E
Deibl
Martina
M
Gastl
Guenther
G
Gunsilius
Eberhard
E
Marth
Christian
C
D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D014408:Biomarkers, Tumor; D017252:CD3 Complex; D051858:Forkhead Transcription Factors; D050856:Interferon Regulatory Factor-1; D007371:Interferon-gamma; D047908:Intracellular Signaling Peptides and Proteins; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C418974:FOXP3 protein, human; C108944:SOCS1 protein, human