Grant: Project Grant

Immunotherapies that help the immune system fight cancer have been approved for the treatment of various cancers and there is hope that this approach will be effective in treating certain types of breast cancer. For example, triple negative breast cancers (TNBC) are a particularly aggressive form of breast cancer, some of which are infiltrated with immune cells ("immune hot") making them ideal for in immune based therapies. However, other classes of TNBC and other subtypes such as HER2, Luminal B and Luminal A breast cancers possess an immunosuppressive tumor microenvironment, in which the anti-tumor properties of immune cells are suppressed ("immune cold"). Thus, one of the major challenges with immunotherapies targeting breast cancer are the "immune cold" tumors, which are resistant to most conventional immunotherapies. Using a genetically engineered mouse model, we have identified a factor known as Chi3L1 that plays a multifaceted role in tumor induction through the generation of immunosuppressive tumor microenvironment. In this CIHR proposal, we will evaluate whether impairing Chi3L1 function can re-sensitize "immune cold" tumors to various immunotherapy approaches.