Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via IL-22
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ABSTRACT:
PROVIDER: PRJNA897928 | ENA |
REPOSITORIES: ENA
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Project description:The crosstalk among the immune system, cancer cells and the tissue microenvironment is fundamental for the emergence of organ-specific niches that facilitate metastasis formation. Here, we studied the involvement of IL-22, which is known to be produced by immune cells and to act on the tissue, in mediating this crosstalk and thus metastasis formation. We found that Il22-deficient mice and mice treated with an IL-22 antibody are protected from liver and lung metastasis formation, while over expression of IL-22 promoted metastasis formation. Mechanistically, IL-22 acted on endothelial cells thereby promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Finally, tissue resident iNKT17 cells were the key source of IL-22 in the liver. Thus, targeting tissue resident immune cells derived IL-22 represents a potential therapeutic target in metastasis formation.
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