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With partners in Belgium, France and Germany, and with our GCI collaborator Dr Morag Park, we are mapping the adaptation of triple-negative breast cancer to chemo-immunotherapy. This project leverages spatial transcriptomics and multiplex analysis of primary and metastatic lesions from 3 large randomized clinical trials.

We recently discovered that blocking or deleting ENT1, the major regulator of extracellular adenosine concentrations, significantly enhanced CD8+ T cell-dependent anti-tumor immunity. Using gene-targeted mice and preclinical cancer models, we are now characterizing the cell-specific function of ENT1 and ENT2 in various immune cell populations.

Using bioinformatics, we discovered Protease-activated receptor-2 (PAR2) as a potential new target to overcome resistance to immune checkpoint inhibitors. PAR2 is a receptor activated by specific tumor proteases and involved in pathophysiological inflammation. We are investigating the impact of PAR2 on tumor immunity using gene-targeted mice and proteomics analysis of human tumors, and will identify patient populations that may benefit from PAR2-targeted therapy.

With collaborators at CHUM and Ottawa Hospital Research Institute, we are defining the immune landscape and functional interactions at single-cell level of rare ovarian cancers. Our goal is to identify new biomarkers for diagnosis and new treatment trajectories, including immunotherapies and antibody-drug conjugates.