Immunity · 2023

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

СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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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

Аннотация

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.

Предметные рубрики MeSH

Animals Mice Endothelial Cells Interleukins Liver Neoplasms Mice, Inbred C57BL Natural Killer T-Cells Colorectal Neoplasms Interleukin-22

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

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Аннотация

Предметные рубрики MeSH