{Reference Type}: Journal Article
{Title}: Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.
{Author}: Giannou AD;Kempski J;Shiri AM;Lücke J;Zhang T;Zhao L;Zazara DE;Cortesi F;Riecken K;Amezcua Vesely MC;Low JS;Xu H;Kaffe E;Garcia-Perez L;Agalioti T;Yamada Y;Jungraithmayr W;Zigmond E;Karstens KF;Steglich B;Wagner J;Konczalla L;Carambia A;Schulze K;von Felden J;May P;Briukhovetska D;Bedke T;Brockmann L;Starzonek S;Lange T;Koch C;Riethdorf S;Pelczar P;Böttcher M;Sabihi M;Huber FJ;Reeh M;Grass JK;Wahib R;Seese H;Stüben BO;Fard-Aghaie M;Duprée A;Scognamiglio P;Plitzko G;Meiners J;Soukou S;Wittek A;Manthey C;Maroulis IC;Arck PC;Perez D;Gao B;Zarogiannis SG;Strowig T;Pasqualini R;Arap W;Gosálvez JS;Kobold S;Prinz I;Guse AH;Tachezy M;Ghadban T;Heumann A;Li J;Melling N;Mann O;Izbicki JR;Pantel K;Schumacher U;Lohse AW;Flavell RA;Gagliani N;Huber S;
{Journal}: Immunity
{Volume}: 56
{Issue}: 1
{Year}: 01 2023 10
{Factor}: 43.474
{DOI}: 10.1016/j.immuni.2022.12.014
{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.