{"doi":"10.1016/j.immuni.2022.12.014","title":"Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22","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.","journal":"Immunity","year":2023,"id":318677,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1026499,"name":"Jan Kempski","orcid":"0000-0001-8867-5077","position":1,"is_corresponding":false},{"id":1026500,"name":"Ahmad Mustafa Shiri","orcid":"0000-0002-9472-0038","position":2,"is_corresponding":false},{"id":1026501,"name":"Jöran Lücke","orcid":"0000-0002-6081-479X","position":3,"is_corresponding":false},{"id":1026502,"name":"Tao Zhang","orcid":"0000-0001-9331-8832","position":4,"is_corresponding":false},{"id":1026503,"name":"Lilan Zhao","orcid":"0000-0001-9862-1785","position":5,"is_corresponding":false},{"id":1026504,"name":"Dimitra E. 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