10.03 Interleukin-22 regulates anti-tumor immunity in mouse models of lung and breast carcinoma

Background High expression of CD155 (poliovirus receptor, PVR) is associated with a poor prognosis lung adenocarcinoma (LUAD) and triple-negative breast cancer (TNBC) patients. When overexpressed, this molecule inhibits the antitumor function NK cytotoxic T cells through binding to its inhibitory co-receptors TIGIT CD96, downregulation stimulatory CD226 (DNAM-1). However, exact mechanism overexpression on tumor remains unclear. Here we demonstrate that interleukin-22 (IL-22), cytokine known promote progression, induces upregulation in mouse models may, thus, inhibit immunity metastasis. Materials Methods To study influence IL-22 immunity, utilize IL-22-deficient animals syngeneic metastatic cancer. For purpose, generated deficient receptor (IL-22R) or cells, constantly express independent natural regulation. Here, determine incidence metastasis cell responses lung, primary site Results We murine upregulate surface upon treatment recombinant IL-22, whereas effect abolished absence IL-22R. Furthermore, have lower burden dramatic increase IFN-γ production NK, and, extent, cells. Moreover, reversed when expressed regulation, which enables metastases animals. Phenotypically, knockout mice higher co-stimulatory CD226, linked potential these Conclusions novel pathway cytokine-mediated where capable inducing therefore, promotes an immunosuppressive microenvironment. This highlights as target for immunotherapy considering complexity CD155-dependent immunoregulatory network. Disclosure Information D. Briukhovetska: None. J. Suarez-Gosalvez: M. Schübel: A. Markota: Jobst: Dörr: F. Märkl: Schwerdtfeger: Öner: Seifert: Gottschlich: S. Endres: Kobold: