biostudies-literatureGiannou ADEuropean Research CouncilHoward Hughes Medical Institute125-142.e12https://www.ebi.ac.uk/biostudies/studies/S-EPMC9839362biostudies-literatureUnknown56(1)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 extravasatiImmunityTissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.PMC9839362756017715271865466Starzonek SGao BGrass JKScognamiglio PSchumacher UCarambia ABedke TMeiners JFlavell RAFard-Aghaie MHuber SKoch CPrinz IBriukhovetska DMelling NShiri AMTachezy MKaffe ELange TLohse AWCortesi FKonczalla LZarogiannis SGvon Felden JJungraithmayr WBottcher MLi JArap WZigmond EDupree AKobold SWagner JXu HIzbicki JRGosalvez JSPasqualini RRiethdorf SMaroulis ICHeumann APlitzko GManthey CZazara DELow JSYamada YSchulze KSoukou SWittek AAmezcua Vesely MCPantel KKarstens KFMann OGarcia-Perez LReeh MSabihi MZhao LPerez DBrockmann LArck PCGagliani NMay PAgalioti TPelczar PGuse AHWahib RGiannou ADSteglich BStrowig THuber FJSeese HKempski JZhang TRiecken KGhadban TStuben BOLucke JfalseTissue 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 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 extravasati2023-01-01T00:00:00Z2023 Jan2026-05-27T22:34:05.003Z2025-04-06T11:11:46.632ZS-EPMC98393623663091110.1016/j.immuni.2022.12.014