IL-23 stabilizes an effector T reg cell program in the tumor microenvironment.

Autor: Wertheimer T; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Zwicky P; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Rindlisbacher L; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Sparano C; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Vermeer M; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., de Melo BMS; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.; Department of Pharmacology, Center for Research in Inflammatory Diseases, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil., Haftmann C; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Rückert T; Department of Internal Medicine I, Hematology, Oncology, and Stem Cell Transplantation, Faculty of Medicine, Medical Centre, University of Freiburg, Freiburg, Germany., Sethi A; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Schärli S; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Huber A; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Ingelfinger F; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Xu C; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Kim D; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Häne P; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Fonseca da Silva A; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Muschaweckh A; Institute for Experimental Neuroimmunology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany., Nunez N; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Krishnarajah S; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Köhler N; Department of Internal Medicine I, Hematology, Oncology, and Stem Cell Transplantation, Faculty of Medicine, Medical Centre, University of Freiburg, Freiburg, Germany.; Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany., Zeiser R; Department of Internal Medicine I, Hematology, Oncology, and Stem Cell Transplantation, Faculty of Medicine, Medical Centre, University of Freiburg, Freiburg, Germany.; Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany., Oukka M; Department of Immunology, University of Washington, Seattle, WA, USA., Korn T; Institute for Experimental Neuroimmunology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Tugues S; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland. tugues@immunology.uzh.ch., Becher B; Department of Inflammation Research, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland. becher@immunology.uzh.ch.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Mar; Vol. 25 (3), pp. 512-524. Date of Electronic Publication: 2024 Feb 14.
DOI: 10.1038/s41590-024-01755-7
Abstrakt: Interleukin-23 (IL-23) is a proinflammatory cytokine mainly produced by myeloid cells that promotes tumor growth in various preclinical cancer models and correlates with adverse outcomes. However, as to how IL-23 fuels tumor growth is unclear. Here, we found tumor-associated macrophages to be the main source of IL-23 in mouse and human tumor microenvironments. Among IL-23-sensing cells, we identified a subset of tumor-infiltrating regulatory T (T reg ) cells that display a highly suppressive phenotype across mouse and human tumors. The use of three preclinical models of solid cancer in combination with genetic ablation of Il23r in T reg cells revealed that they are responsible for the tumor-promoting effect of IL-23. Mechanistically, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of effector T reg cells involving the transcription factor Foxp3. Our data support that targeting the IL-23/IL-23R axis in cancer may represent a means of eliciting antitumor immunity.
(© 2024. The Author(s).)
Databáze: MEDLINE
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