Cells with hypermutation phenotypes harbor an initial growth advantage to form primary tumors. However, this group of tumors produces more tumor-specific antigens that evoke immune responses. Contrarily, tumors that exhibit a low mutator phenotype avoid de novo mutations that would be deleterious to cellular fitness and, most importantly, evade immune surveillance. As a result, these patients harbor weaker immunogenic phenotypes with immune cell-poor tumor microenvironments, limiting the response rate to immunotherapies.

This team’s main objective is to identify how DNA damage response (DDR) shapes the tumor microenvironment. Using colorectal cancer as a model, this team will investigate the molecular pathways altered in immunogenic and non-immunogenic tumor clusters. The main aim of the project will be to identify canonical and non-canonical roles of DDR molecules involved in tumor immunity. Our final goal is to design new therapeutic targets that promote a favorable tumor microenvironment for immunotherapies.