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

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...

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Detalles Bibliográficos
Autores principales: Giannou, Anastasios D., Kempski, Jan, Shiri, Ahmad Mustafa, Lücke, Jöran, Zhang, Tao, Zhao, Lilan, Zazara, Dimitra E., Cortesi, Filippo, Riecken, Kristoffer, Amezcua Vesely, Maria Carolina, Low, Jun Siong, Xu, Hao, Kaffe, Eleanna, Garcia-Perez, Laura, Agalioti, Theodora, Yamada, Yoshito, Jungraithmayr, Wolfgang, Zigmond, Ehud, Karstens, Karl-Frederick, Steglich, Babett, Wagner, Jonas, Konczalla, Leonie, Carambia, Antonella, Schulze, Kornelius, von Felden, Johann, May, Peter, Briukhovetska, Daria, Bedke, Tanja, Brockmann, Leonie, Starzonek, Sarah, Lange, Tobias, Koch, Claudia, Riethdorf, Sabine, Pelczar, Penelope, Böttcher, Marius, Sabihi, Morsal, Huber, Francis J., Reeh, Matthias, Grass, Julia Kristin, Wahib, Ramez, Seese, Hannes, Stüben, Björn-Ole, Fard-Aghaie, Mohammad, Duprée, Anna, Scognamiglio, Pasquale, Plitzko, Gabriel, Meiners, Jan, Soukou, Shiwa, Wittek, Agnes, Manthey, Caroline, Maroulis, Ioannis C., Arck, Petra C., Perez, Daniel, Gao, Bin, Zarogiannis, Sotirios G., Strowig, Till, Pasqualini, Renata, Arap, Wadih, Gosálvez, Javier Suárez, Kobold, Sebastian, Prinz, Immo, Guse, Andreas H., Tachezy, Michael, Ghadban, Tarik, Heumann, Asmus, Li, Jun, Melling, Nathaniel, Mann, Oliver, Izbicki, Jakob R., Pantel, Klaus, Schumacher, Udo, Lohse, Ansgar W., Flavell, Richard A., Gagliani, Nicola, Huber, Samuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839362/
https://www.ncbi.nlm.nih.gov/pubmed/36630911
http://dx.doi.org/10.1016/j.immuni.2022.12.014
Descripción
Sumario: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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