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Giannou, A.D.* ; Kempski, J.* ; Shiri, A.M.* ; Lücke, J.* ; Zhang, T.* ; Zhao, L.* ; Zazara, D.E.* ; Cortesi, F.* ; Riecken, K.* ; Amezcua Vesely, M.C.* ; Low, J.S.* ; Xu, H.* ; Kaffe, E.* ; Garcia-Perez, L.* ; Agalioti, T.* ; Yamada, Y.* ; Jungraithmayr, W.* ; Zigmond, E.* ; Karstens, K.F.* ; Steglich, B.* ; Wagner, J.* ; Konczalla, L.* ; Carambia, A.* ; Schulze, K.* ; von Felden, J.* ; May, P.* ; Briukhovetska, D.* ; Bedke, T.* ; Brockmann, L.* ; Starzonek, S.* ; Lange, T.* ; Koch, C.* ; Riethdorf, S.* ; Pelczar, P.* ; Böttcher, M.* ; Sabihi, M.* ; Huber, F.J.* ; Reeh, M.* ; Grass, J.K.* ; Wahib, R.* ; Seese, H.* ; Stüben, B.O.* ; Fard-Aghaie, M.* ; Duprée, A.* ; Scognamiglio, P.* ; Plitzko, G.* ; Meiners, J.* ; Soukou, S.* ; Wittek, A.* ; Manthey, C.* ; Maroulis, I.C.* ; Arck, P.C.* ; Perez, D.* ; Gao, B.* ; Zarogiannis, S.G.* ; Strowig, T.* ; Pasqualini, R.* ; Arap, W.* ; Gosálvez, J.S.* ; Kobold, S. ; Prinz, I.* ; Guse, A.H.* ; Tachezy, M.* ; Ghadban, T.* ; Heumann, A.* ; Li, J.* ; Melling, N.* ; Mann, O.* ; Izbicki, J.R.* ; Pantel, K.* ; Schumacher, U.* ; Lohse, A.W.* ; Flavell, R.A.* ; Gagliani, N.* ; Huber, S.*

Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.

Immunity 56, 125-142.e12 (2023)
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During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Anpep ; Il-22 ; Cancer Cell Extravasation ; Endothelial Cells ; Extravasation ; Metastasis ; Metastasis Formation ; Tissue Resident Cells; T-cells; Mouse Model; Immune Cells; Colon-cancer; Receptor; Th17; Il-22bp; Surveillance; Activation; Dynamics
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1074-7613
e-ISSN 1097-4180
Journal Immunity
Quellenangaben Volume: 56, Issue: 1, Pages: 125-142.e12 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Reviewing status Peer reviewed
Institute(s) Unit for Clinical Pharmacology (KKG-EKLiP)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-522100-001
Grants European Research Council
Else Kroner Memorial Stipendium
Erich und Gertrud Roggenbuck-Stiftung
Hamburger Krebsgesellschaft Stiftung
Jung Foundation for Science and Research
Howard Hughes Medical Institute
Alexander von Humboldt Stiftung for an Experienced Researcher Fellowship
AIRC
European Union
Deutsche Forschungsgemeinschaft (DFG)
Deutsche Krebshilfe
ERC Advanced Investigator Grant
DOI 10.1016/j.immuni.2022.12.014
WOS ID 000941200600001
Scopus ID 85146043104
PubMed ID 36630911
Erfassungsdatum 2023-01-17
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