Exploring the role of CAR in tumour-immune cell interactions

Our recent unpublished data demonstrates a further important role for CAR and PKC in promoting lung cancer cell proliferation in vitro and in vivo. In this context, we have shown that phosphorylated CAR is also important for maintaining junctions between proliferating human lung cancer cells and this in turn promotes optimal signaling downstream of epidermal growth factor receptor (EGFR) to perpetuate cell division. CAR has also been shown to bind to another of the JAM family proteins, JAML, that is expressed on the surface of leukocytes and this facilitates leukocyte transmigration andactivation. We have shown that CAR acts downstream of TNF - induced signalling to promote trans - epithelial migration of immune cells both in vitro and in vivo. However, it remains unclear whether CAR:JAM-L triggers changes in the epithelial cell junction tofacilitate trans-epithelial migration (TEpM) and whether this role extends to the tumour microenvironment, where CAR is upregulated. The aim of this project is to define how CAR depletion from tumour cells in non-immunocompromised mice impacts tumour growth, immune cell infiltration into tumours and stromal organization.