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oai:repisalud.isciii.es:20.500.12105/253612025-12-18T12:59:50Zcom_20.500.12105_2273com_20.500.12105_2202col_20.500.12105_19571

00925njm 22002777a 4500 dc Briukhovetska, Daria author Suarez-Gosalvez, Javier author Voigt, Cornelia author Markota, Anamarija author Giannou, Anastasios D author Schübel, Maryam author Jobst, Jakob author Zhang, Tao author Dörr, Janina author Märkl, Florian author Majed, Lina author Müller, Philipp Jie author May, Peter author Gottschlich, Adrian author Tokarew, Nicholas author Lücke, Jöran author Oner, Arman author Schwerdtfeger, Melanie author Andreu-Sanz, David author Grünmeier, Ruth author Seifert, Matthias author Michaelides, Stefanos author Hristov, Michael author König, Lars M author Cadilha, Bruno Loureiro author Mikhaylov, Oleg author Anders, Hans-Joachim author Rothenfusser, Simon author Flavell, Richard A author Cerezo-Wallis, Daniela author Tejedo, Cristina author Soengas, MS author Bald, Tobias author Huber, Samuel author Endres, Stefan author Kobold, Sebastian author 2023-01-10 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. Immunity . 2023 Jan 10;56(1):143-161 Immunity 36630913 https://hdl.handle.net/20.500.12105/25361 CD155 CD226 NK cells PVR T helper breast carcinoma interleukin-22 lung adenocarcinoma metastasis poliovirus receptor T cell-derived interleukin-22 drives the expression of CD155 by cancer cells to suppress NK cell function and promote metastasis.