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

• DOI: 10.1016/j.immuni.2022.12.014
• Publication Date: 2023-01-10T18:10:36Z
• Authors: Anastasios D. Gia...; Jan Kempski; Ahmad Mustafa Shiri; Jöran Lücke; Tao Zhang; Lilan Zhao; Dimitra E. Zazara; Filippo Cortesi; Kristoffer Riecken; Maria Carolina Am...; Jun Siong Low; Hao Xu; Eleanna Kaffe; Laura Garcia-Perez; Theodora Agalioti; Yoshito Yamada; Wolfgang Jungrait...; Ehud Zigmond; Karl-Frederick Ka...; Babett Steglich; Jonas Wagner; Leonie Konczalla; Antonella Carambia; Kornelius Schulze; Johann von Felden; Peter May; Daria Briukhovetska; Tanja Bedke; Leonie Brockmann; Sarah Starzonek; Tobias Lange; Claudia Koch; Sabine Riethdorf; Penelope Pelczar; Marius Böttcher; Morsal Sabihi; Francis J. Huber; Matthias Reeh; Julia Kristin Grass; Ramez Wahib; Hannes Seese; Björn-Ole Stüben; Mohammad Fard-Aghaie; Anna Duprée; Pasquale Scognami...; Gabriel Plitzko; Jan Meiners; Shiwa Soukou; Agnes Wittek; Caroline Manthey; Ioannis C. Maroulis; Petra C. Arck; Daniel Perez; Bin Gao; Sotirios G. Zarog...; Till Strowig; Renata Pasqualini; Wadih Arap; Javier Suárez Gos...; Sebastian Kobold; Immo Prinz; Andreas H. Guse; Michael Tachezy; Tarik Ghadban; Asmus Heumann; Jun Li; Nathaniel Melling; Oliver Mann; Jakob R. Izbicki; Klaus Pantel; Udo Schumacher; Ansgar W. Lohse; Richard A. Flavell; Nicola Gagliani; Samuel Huber
• Keywords: Extravasation

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice treated an antibody were protected from colon-cancer-derived liver lung metastasis formation, while overexpression promoted Mechanistically, acted endothelial cells, permeability cell transmigration via induction aminopeptidase N. Multi-parameter flow cytometry single-cell sequencing immune isolated during extravasation into revealed iNKT17 as source IL-22. iNKT-cell-deficient exhibited reduced metastases, which was reversed by injection wild type, not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT resident, demonstrated parabiosis. Thus, may present a therapeutic for prevention