The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer.
Dominik Wolf,Anna Maria Wolf,Holger Rumpold,Heidi Fiegl,Alain G. Zeimet,Elisabeth Müller-Holzner,Martina Deibl,Guenther Gastl,Eberhard Gunsilius,Christian Marth +9 more
TLDR
High expression levels of FoxP3 might represent a surrogate marker for an immunosuppressive milieu contributing to tumor immune escape and strategies selectively depleting Treg might improve the antitumor activity of endogenously arising tumor-reactive T cells and immunotherapies using vaccines or antibodies.Abstract:
Purpose: 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-γ. Experimental Design: 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-γ-, CD3-, IRF-1-, SOCS-1-, HER-2-, and iNOS expression as well as patients9 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-γ, 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.read more
Citations
More filters
Journal ArticleDOI
Epigenetic Control of the foxp3 Locus in Regulatory T Cells
Stefan Floess,Jennifer Freyer,Christiane Siewert,Udo Baron,Sven Olek,Julia K. Polansky,Kerstin Schlawe,Hyun-Dong Chang,Tobias Bopp,Edgar Schmitt,Stefan Klein-Hessling,Edgar Serfling,Alf Hamann,Jochen Huehn +13 more
TL;DR: The data suggest that expression of Foxp3 must be stabilized by epigenetic modification to allow the development of a permanent suppressor cell lineage, a finding of significant importance for therapeutic applications involving induction or transfer of Tregs and for the understanding of long-term cell lineage decisions.
Journal ArticleDOI
DNA Demethylation in the Human FOXP3 Locus Discriminates Regulatory T Cells From Activated FOXP3(+) Conventional T Cells
Udo Baron,Stefan Floess,Georg Wieczorek,Katrin Baumann,Andreas Grützkau,Jun Dong,Andreas Thiel,Tina J. Boeld,Petra Hoffmann,Matthias Edinger,Ivana Türbachova,Alf Hamann,Sven Olek,Jochen Huehn +13 more
TL;DR: It is concluded that FOXP3 DNA demethylation constitutes the most reliable criterion for natural Treg available at present.
Journal ArticleDOI
Immune therapy for cancer.
Michael Dougan,Glenn Dranoff +1 more
TL;DR: Novel approaches to immune-based cancer treatment strive to augment antitumor immune responses by expanding tumor-reactive T cells, providing exogenous immune-activating stimuli, and antagonizing regulatory pathways that induce immune tolerance.
Journal ArticleDOI
Tregs and rethinking cancer immunotherapy
TL;DR: CD4+CD25+ Tregs are one mechanism of tumor-driven immune evasion that provide prototypical targets for testing novel anticancer treatment strategies within the newer paradigm that predicts that reducing tumor- driven immune suppression will be clinically beneficial.
Journal ArticleDOI
Sunitinib Reverses Type-1 Immune Suppression and Decreases T-Regulatory Cells in Renal Cell Carcinoma Patients
James H. Finke,Brian I. Rini,Joanna Ireland,Patricia Rayman,Amy Richmond,Ali Reza Golshayan,Laura S. Wood,Paul Elson,Jorge A. Garcia,Robert Dreicer,Ronald M. Bukowski +10 more
TL;DR: The demonstration that sunitinib improved type-1 T-cell cytokine response in mRCC patients while reducing Treg function provides a basis for the rational combination of sunit inib and immunotherapy in m RCC.
References
More filters
Journal ArticleDOI
A new mathematical model for relative quantification in real-time RT-PCR.
TL;DR: This study enters into the particular topics of the relative quantification in real-time RT-PCR of a target gene transcript in comparison to a reference gene transcript and presents a new mathematical model that needs no calibration curve.
Journal ArticleDOI
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
TL;DR: Foxp3, which encodes a transcription factor that is genetically defective in an autoimmune and inflammatory syndrome in humans and mice, is specifically expressed in naturally arising CD4+ regulatory T cells and retroviral gene transfer of Foxp3 converts naïve T cells toward a regulatory T cell phenotype similar to that of naturally occurring CD4+.
Journal ArticleDOI
Foxp3 programs the development and function of CD4 + CD25 + regulatory T cells
TL;DR: It is reported that the forkhead transcription factor Foxp3 is specifically expressed in CD4+CD25+ regulatory T cells and is required for their development and function and ectopic expression ofFoxp3 confers suppressor function on peripheral CD4-CD25− T cells.
Journal ArticleDOI
Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.
TL;DR: The authors showed that CD4+CD25+ cells contribute to maintaining self-tolerance by downregulating immune response to self and non-self Ags in an Ag-nonspecific manner, presumably at the T cell activation stage.
Journal ArticleDOI
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.
Tyler J. Curiel,George Coukos,Linhua Zou,Xavier Alvarez,Pui Cheng,Peter Mottram,Melina Evdemon-Hogan,Jose R. Conejo-Garcia,Lin Zhang,Matthew E. Burow,Yun Zhu,Shuang Wei,Ilona Kryczek,Ben Daniel,Alan N. Gordon,Leann Myers,Andrew A. Lackner,Mary L. Disis,Keith L. Knutson,Lieping Chen,Weiping Zou +20 more
TL;DR: It is shown, in detailed studies of CD4+CD25+FOXP3+ Treg cells in 104 individuals affected with ovarian carcinoma, that human tumor T Reg cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo.
Related Papers (5)
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.
Tyler J. Curiel,George Coukos,Linhua Zou,Xavier Alvarez,Pui Cheng,Peter Mottram,Melina Evdemon-Hogan,Jose R. Conejo-Garcia,Lin Zhang,Matthew E. Burow,Yun Zhu,Shuang Wei,Ilona Kryczek,Ben Daniel,Alan N. Gordon,Leann Myers,Andrew A. Lackner,Mary L. Disis,Keith L. Knutson,Lieping Chen,Weiping Zou +20 more