Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22
Abstract: 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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Immunity. - 56, 1 (2023) , 125-142.e12, ISSN: 1097-4180
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
-
Universität
- (wann)
-
2023
- Urheber
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Giannou, Anastasios D.
Kempski, Jan Michael
Shiri, Ahmad Mustafa
Jungraithmayr, Wolfgang
Huber Lindenberger, Samuel
- DOI
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10.1016/j.immuni.2022.12.014
- URN
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urn:nbn:de:bsz:25-freidok-2332059
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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14.08.2025, 10:49 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Giannou, Anastasios D.
- Kempski, Jan Michael
- Shiri, Ahmad Mustafa
- Jungraithmayr, Wolfgang
- Huber Lindenberger, Samuel
- Universität
Entstanden
- 2023
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