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T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis.

Immunity

Authors: Daria Briukhovetska, Javier Suarez-Gosalvez, Cornelia Voigt, Anamarija Markota, Anastasios D Giannou, Maryam Schübel, Jakob Jobst, Tao Zhang, Janina Dörr, Florian Märkl, Lina Majed, Philipp Jie Müller, Peter May, Adrian Gottschlich, Nicholas Tokarew, Jöran Lücke, Arman Oner, Melanie Schwerdtfeger, David Andreu-Sanz, Ruth Grünmeier, Matthias Seifert, Stefanos Michaelides, Michael Hristov, Lars M König, Bruno Loureiro Cadilha, Oleg Mikhaylov, Hans-Joachim Anders, Simon Rothenfusser, Richard A Flavell, Daniela Cerezo-Wallis, Cristina Tejedo, María S Soengas, Tobias Bald, Samuel Huber, Stefan Endres, Sebastian Kobold

Although T cells can exert potent anti-tumor immunity, a subset of T helper (Th) cells producing interleukin-22 (IL-22) in breast and lung tumors is linked to dismal patient outcome. Here, we examined the mechanisms whereby these T cells contribute to disease. In murine models of lung and breast cancer, constitutional and T cell-specific deletion of Il22 reduced metastases without affecting primary tumor growth. Deletion of the IL-22 receptor on cancer cells decreases metastasis to a degree similar to that seen in IL-22-deficient mice. IL-22 induced high expression of CD155, which bound to the activating receptor CD226 on NK cells. Excessive activation led to decreased amounts of CD226 and functionally impaired NK cells, which elevated the metastatic burden. IL-22 signaling was also associated with CD155 expression in human datasets and with poor patient outcomes. Taken together, our findings reveal an immunosuppressive circuit activated by T cell-derived IL-22 that promotes lung metastasis.

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

PMID: 36630913

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