Manipulating STING signalling pathways in VHL mutant renal carcinoma cells to regulate T cell function

We will use an autochthonous mouse model of clear cell renal cell carcinoma (ccRCC) and human ccRCC cell lines to define the connection between genomic instability induced by mutation of the VHL gene, STING-mediated inflammatory signalling and the tumour immune microenvironment. Using Sting mutant mice we will investigate the contribution of STING activity to ccRCC development. We will therapeutically test chemotherapeutic agents and STING activators and inhibitors for their ability to modulate the ccRCC immune microenvironment and for efficacy in combination with immune checkpoint blockade.