Immune-regulatory functions of Group 2 Innate Lymphoid cells in cancer (360G-Wellcome-204622_Z_16_Z)

Anti-tumour 'type-1' immunity is driven by NK cells and cytotoxic CD8 T cells, while T helper type-2 (Th2) cells are associated with a pro-tumourigenic phenotype. Group 2 innate lymphoid cells (ILC2) are the innate counterpart of Th2 cells, and are locally activated by epithelial derived alarmins. While recognised as central orchestrators of 'type-2' inflammation in allergies, there is no evidence for their importance in shaping a pro-tumourigenic environment, despite the known roles of alarmins in tumourigenesis. My preliminary data reports the presence and profound enrichment of ILC2 in pancreatic intraepithelial neoplasias (PanIN) as they progress to pancreatic ductal adenocarinoma in P48-Cre LSL-KrasG12D (KC) mice. I will resolve the role of ILC2 in pancreatic carcinogenesis using an orthotopic implantation model in conjunction with next-generation ILC2-targeted reagents and intravital imaging. Secondly, I present preliminary data that suggests a negative-feedback mechanism by which lung ILC2 dampen the anti-tumour immune function of NK cells. I will use exclusive ILC2-targeted reagents to resolve this mechanism, and its effect on lung metastasis formation. As tissue resident immune-modulators, ILC2 may provide a critical new target in cancer therapy.