title: Suppression of intratumoral CCL22 by type i interferon inhibits migration of regulatory T cells and blocks cancer progression.
abstract: The chemokine CCL22 is abundantly expressed in many types of cancer and is instrumental for intratumoral recruitment of regulatory T cells (Treg), an important subset of immunosuppressive and tumor-promoting lymphocytes. In this study, we offer evidence for a generalized strategy to blunt Treg activity that can limit immune escape and promote tumor rejection. Activation of innate immunity with Toll-like receptor (TLR) or RIG-I-like receptor (RLR) ligands prevented accumulation of Treg in tumors by blocking their immigration. Mechanistic investigations indicated that Treg blockade was a consequence of reduced intratumoral CCL22 levels caused by type I IFN. Notably, stable expression of CCL22 abrogated the antitumor effects of treatment with RLR or TLR ligands. Taken together, our findings argue that type I IFN blocks the Treg-attracting chemokine CCL22 and thus helps limit the recruitment of Treg to tumors, a finding with implications for cancer immunotherapy.
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany. Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Anz
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Rapp
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany. Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Eiber
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
authors.forename: Viktor H
authors.initials: VH
authors.lastname: Koelzer
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
authors.forename: Raffael
authors.initials: R
authors.lastname: Thaler
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: Haubner
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Knott
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nagel
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Golic
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
authors.forename: Gabriela M
authors.initials: GM
authors.lastname: Wiedemann
authors.affiliation: Institute of Molecular Medicine, Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Bauernfeind
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Wurzenberger
authors.affiliation: Institute of Molecular Medicine, Universitätsklinikum Bonn, Bonn, Germany. Institute of Molecular Medicine, Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
authors.affiliation: Department of Obstetrics and Gynecology, Ulm University Medical Centre, Ulm, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Scholz
authors.affiliation: Department of Pathology, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Rothenfusser
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany. endres@lmu.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
authors.affiliation: Center of Integrated Protein Science Munich (CIPS-M), Division of Clinical Pharmacology, Klinikum der Universität München, Munich, Germany. Department of Medicine, University of Fribourg, Fribourg, Switzerland.
authors.forename: Carole
authors.initials: C
authors.lastname: Bourquin
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D054422:Chemokine CCL22 / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D061986:MCF-7 Cells; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000637:transplantation; D019139:Tumor Escape / Q000276:immunology
chemical_list: C515482:CCL22 protein, human; D054422:Chemokine CCL22; D007370:Interferon Type I