title: Transient ablation of regulatory T cells improves antitumor immunity in colitis-associated colon cancer.
abstract: Regulatory T cells (Treg) are supportive to cancer development in most tissues, but their role in colitis-associated colon cancer (CAC) remains unclear. In this study, we investigated the role of CD4(+)Foxp3(+) Treg in a mouse model of CAC and in patients with colon cancer. These Treg were increased strongly in number in a mouse model of CAC and in the peripheral blood of patients with colon cancer, exhibiting an activated phenotype as defined by elevated expression of GARP, CD103, CTLA-4, and IL10, along with an increased suppressive effect on the proliferation and Th1 cytokine expression of CD4(+)CD25(-) responder T cells ex vivo. Transient ablation of CD4(+)Foxp3(+) Treg during tumor development in the CAC model suppressed tumor outgrowth and distribution, accompanied by an increased number of CD8(+)IFNγ/granzyme B-producing effector T cells. Conversely, inactivation of IL10 in Treg did not elevate the antitumor response but instead further boosted tumor development. Our results establish a tumor-promoting function for Treg during CAC formation, but they also suggest that a selective, transient ablation of Treg can evoke antitumor responses, with implications for immunotherapeutic interventions in patients with CAC.
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Pastille
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Bardini
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Fleissner
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Adamczyk
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Frede
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Munisch
authors.initials: M
authors.lastname: Wadwa
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Dorthe
authors.initials: D
authors.lastname: von Smolinski
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Kasper
authors.affiliation: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Medicine, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Institute of Veterinary Pathology, Freie Universität Berlin, Berlin, Germany.
authors.forename: Achim D
authors.initials: AD
authors.lastname: Gruber
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany. German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
authors.affiliation: Department of Experimental Immunology, Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.affiliation: Institute for Immunology, Technische Universität Dresden, Medical Faculty Carl Gustav Carus, Dresden, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Roers
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Werner
authors.initials: W
authors.lastname: Müller
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hansen
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany. astrid.westendorf@uk-essen.de.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Westendorf
mesh_terms: D000818:Animals; D003092:Colitis / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*