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

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

IMMUNITY

CELL PRESS

Año: 2023 vol. 56 p. 125 - 125

1074-7613

uring 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 natur