Grant: Project Grant

Over the past 10 years, the most significant advance in cancer treatment has been the development of "immunotherapy", in particular of agents capable of blocking molecules such as PD-1 and CTLA-4, which suppress the functions of immune cells known as "T cells". Blocking of PD-1 or CTLA-4 by drugs was found to cure many patients with cancer. However, not all cancer patients respond to blocking agents targeting PD-1 or CTLA-4. As a result, significant efforts have been directed at identifying additional molecules that could be new targets for immunotherapy, in particular on immune cells other than T cells. These efforts led to the identification of the SIRPa-CD47 molecules that suppress the ability of immune cells known as "macrophages" to eat and destroy cancer cells. Over the recent few years, it was reported that treatment of cancer patients with blockers of SIRPa-CD47 augment the ability of their macrophages to destroy cancer cells and can result in complete remissions in a subset of patients. Based on these exciting results, we have been interested in understanding how macrophages eat cancer cells, and how this capacity can be further augmented by blockade of SIRPa-CD47, and by blockade of other molecules such as CD200R1 and PSGL-1. The purpose of this proposal is to understand better how SIRPa-CD47, CD200R1 and PSGL-1 operate and how they can be targeted for better immunotherapy treatments against cancer.