Grant: CIHR Fellowship

Tumor-infiltrating T cells are critical participants in controlling the growth, aggressiveness, and lethality of many cancers. These immune cells act contextually within the tumor to either promote remission or facilitate cancer growth. This is exemplified in the recent successes of the immunotherapies anti-CTLA-4 and anti-PD-1, which modulate tumor-infiltrating T cell function to induce a protective response. In these treatments, subsets of patients experience remarkable tumor regression. However, the dominant molecular pathways preventing tumor-infiltrating T cell mediated tumor rejection remain obscure. Identification and detailed investigation of these pathways is of fundamental importance in order to understand immune responses to aberrant tissue growth. Recently, levels of the protein layilin have been found to highly correlate with poor clinical outcomes in multiple cancers. Our laboratory has independently observed elevated layilin on tumor-infiltrating T cells in melanoma patients. As there is a critical lack of knowledge regarding layilin's biological function we propose to comprehensively dissect the functional role of layilin on tumor-infiltrating T cells. To accomplish this goal we have generated novel tools that allow us to modulate layilin levels in both human and mouse model systems. Notably, our project has the potential to unveil layilin as a master target for immunotherapy since it is simultaneously implicated in both protective and deleterious T cell responses, as well as the intrinsic aggressiveness of cancer cells themselves.