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

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 can...

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Detalles Bibliográficos
Autores: Briukhovetska, Daria, Suarez-Gosalvez, Javier, Voigt, Cornelia, Markota, Anamarija, Giannou, Anastasios D, Schübel, Maryam, Jobst, Jakob, Zhang, Tao, Dörr, Janina, Märkl, Florian, Majed, Lina, Müller, Philipp Jie, May, Peter, Gottschlich, Adrian, Tokarew, Nicholas, Lücke, Jöran, Oner, Arman, Schwerdtfeger, Melanie, Andreu-Sanz, David, Grünmeier, Ruth, Seifert, Matthias, Michaelides, Stefanos, Hristov, Michael, König, Lars M, Cadilha, Bruno Loureiro, Mikhaylov, Oleg, Anders, Hans-Joachim, Rothenfusser, Simon, Flavell, Richard A, Cerezo-Wallis, Daniela, Tejedo, Cristina, Soengas, MS, Bald, Tobias, Huber, Samuel, Endres, Stefan, Kobold, Sebastian
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/25361
Acceso en línea:https://hdl.handle.net/20.500.12105/25361
Access Level:acceso abierto
Palabra clave:CD155
CD226
NK cells
PVR
T helper
breast carcinoma
interleukin-22
lung adenocarcinoma
metastasis
poliovirus receptor
Descripción
Sumario: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.

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