ArticleImmunity2023
T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis.
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Article in Immunity, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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57 citing papers in PubMed, 81 citations in OpenAlex.
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- A Novel Class of Multi-substituted Diaryl Scaffold Derivatives Inhibit Glioblastoma Progression by Targeting CD155.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
36 authors at 7 institutions in 3 countries.
Daria BriukhovetskaDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Javier Suarez-GosalvezDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Cornelia VoigtDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Anamarija MarkotaDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Anastasios D GiannouSection of Molecular Immunology and Gastroenterology, I. Department of Medicine, and Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Maryam SchübelDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Jakob JobstDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Tao ZhangSection of Molecular Immunology and Gastroenterology, I. Department of Medicine, and Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Janina DörrDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Florian MärklDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Lina MajedDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Philipp Jie MüllerDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Peter MayDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Adrian GottschlichDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Nicholas TokarewDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Jöran LückeSection of Molecular Immunology and Gastroenterology, I. Department of Medicine, and Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Arman OnerDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Melanie SchwerdtfegerDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
David Andreu-SanzDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Ruth GrünmeierDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Matthias SeifertDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Stefanos MichaelidesDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Michael HristovInstitute for Cardiovascular Prevention (IPEK), University Hospital, Klinikum der Universität München, Munich, Germany.
Lars M KönigDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Bruno Loureiro CadilhaDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany.
Oleg MikhaylovTwentyBN, 10245 Berlin, Germany.
Hans-Joachim AndersDivision of Nephrology, Department of Medicine IV, Klinikum der Universität München, 80337 Munich, Germany.
Simon RothenfusserDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany; Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), 85764 Neuherberg, Germany.
Richard A FlavellDepartment of Immunobiology, School of Medicine, Yale University, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA.
Daniela Cerezo-WallisMelanoma Laboratory, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
Cristina TejedoMelanoma Laboratory, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
María S SoengasMelanoma Laboratory, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), 28029 Madrid, Spain.
Tobias BaldInstitute of Experimental Oncology, Medical Faculty, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany.
Samuel HuberSection of Molecular Immunology and Gastroenterology, I. Department of Medicine, and Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Stefan EndresDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany; Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), 85764 Neuherberg, Germany; Center for Translational Cancer Research (DKTK), Partner Site Munich, 80336 Munich, Germany.
Sebastian KoboldDivision of Clinical Pharmacology, Klinikum der Universität München, 80337 Munich, Germany; Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), 85764 Neuherberg, Germany; Center for Translational Cancer Research (DKTK), Partner Site Munich, 80336 Munich, Germany. Electronic address: sebastian.kobold@med.uni-muenchen.de.
LMU Klinikum · DEUniversität Hamburg · DEHelmholtz Zentrum München · DESpanish National Cancer Research Centre · ESHoward Hughes Medical Institute · USInstitut für Tier-, Natur- und Umweltethik · DEUniversity Hospital Bonn · DE
Funding
Howard Hughes Medical Institute
Abstract
Although T cells can exert potent anti-tumor immunity, a subset of T helper (Th) cells producing interleukin-22 (IL-22) in breast and lung tumors is linked to dismal patient outcome. Here, we examined the mechanisms whereby these T cells contribute to disease. In murine models of lung and breast cancer, constitutional and T cell-specific deletion of Il22 reduced metastases without affecting primary tumor growth. Deletion of the IL-22 receptor on cancer cells decreases metastasis to a degree similar to that seen in IL-22-deficient mice. IL-22 induced high expression of CD155, which bound to the activating receptor CD226 on NK cells. Excessive activation led to decreased amounts of CD226 and functionally impaired NK cells, which elevated the metastatic burden. IL-22 signaling was also associated with CD155 expression in human datasets and with poor patient outcomes. Taken together, our findings reveal an immunosuppressive circuit activated by T cell-derived IL-22 that promotes lung metastasis.
Indexed as
InterleukinsNeoplasmsReceptors, VirusT-Lymphocytes, Helper-InducerAnimalsAntigens, Differentiation, T-LymphocyteHumansInterleukin-22Killer Cells, NaturalMiceProtein BindingAntigens, Differentiation, T-LymphocyteInterleukin-22Interleukinspoliovirus receptorReceptors, Virusbreast carcinomaCD155CD226interleukin-22lung adenocarcinomametastasisNK cellspoliovirus receptorPVRT helper
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