Crosspresentation of dead cell-associated antigens in immunity to cancer

Dendritic cells are able to alert T cells to cancers, initiating anti-cancer immunity. Key to this process is a receptor called DNGR-1 in the dendritic cells that sniffs out dead cancer cells. We propose to understand how this is regulated and whether we can harness it for cancer therapy. Interestingly, the ability of DNGR-1 to sniff out dead cell fragments is blunted by a protein called secreted gelsolin. We propose to test whether production of secreted gelsolin by cancers is used to evade DNGR-1 attention and immunity. In parallel, we will also test whether arming a large number of immune cells with DNGR-1 might help in "sharing the load" so that rare dendritic cells in tumours are not overwhelmed by lots of dead cancer cells. The studies we propose will help understand how the immune system responds to tumours and provide us with new classes of cancer immunotherapeutics.