Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Immunity (Cambridge, Mass.), 2023-01, Vol.56 (1), p.125-142.e12

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Il22-deficient mice are protected against metastasis formation•IL-22 neutralization blocks cancer cell extravasation•IL-22 acts on endothelial cells, promoting cancer cell extravasation via ANPEP induction•Tissue resident iNKT17 cells are the key IL-22 source during cancer cell extravasation Interleukin-22 (IL-22) is produced by immune cells and promotes tissue repair and regeneration; however, in malignancy, IL-22 can promote tumor growth. Giannou et al. find that tissue resident iNKT17 cells produce IL-22 and promote cancer cell extravasation through regulation of aminopeptidase N. Neutralization of IL-22 inhibits metastasis formation, suggesting therapeutic avenues for cancer treatment.