Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22
Beteiligte Einrichtungen
- Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie
- I. Medizinische Klinik und Poliklinik
- Institut für Biochemie und Molekulare Zellbiologie
- Klinik und Poliklinik für Geburtshilfe und Pränatalmedizin
- Interdisziplinäre Klinik und Poliklinik für Stammzelltransplantation
- Institut für Anatomie und Experimentelle Morphologie
- Institut für Tumorbiologie
- Institut für Systemimmunologie
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.
Bibliografische Daten
Originalsprache | Englisch |
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ISSN | 1074-7613 |
DOIs | |
Status | Veröffentlicht - 10.01.2023 |
Anmerkungen des Dekanats
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
PubMed | 36630911 |
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