Research Projects

The immune system in healthy individuals can limit cancer development by relying on immune cells like CD8+ effector cytotoxic T lymphocytes (CTLs) that can directly recognize and kill tumour cells. To launch an effective immune response against a solid tumour, CTLs must travel to the tumour and precisely recognize and react to tumour cell-derived biochemical signals within the tumour microenvironment. Boosting CTL function is a fundamental component of tumour immunotherapy and is used in clinical settings as a safer and more effective alternative to chemotherapy. However, immunosuppressive microenvironments within tumours inhibit CTL infiltration and function. This is one of the primary reasons why most tumour immunotherapies targeting CTL function either fail or do not provide lasting benefits in most patients and most types of cancer. This proposal aims to close this knowledge gap from a cell biological perspective by investigating the fundamental mechanisms that allow or limit tumour infiltration by CTLs. The key step for CTL infiltration in healthy tissues is via cell-cell adhesions with endothelial cells of the vascular wall (VEC), followed by trans-endothelial migration and eventual extravasation into the tissue parenchyma. The study will use state-of-the-art microscopic methods to visualize molecular events at the CTL-VEC contact interface and tissue level changes in the tumour microenvironments leading up T cell infiltration within solid tumours and investigate how they are constrained by suppressive cues from the tumour.