Immune cell complexity in the tumor microenvironment of breast cancer

Abstract

My PhD studies focused on understanding the role of macrophages, a type of immune cells which are abundantly present in several tumor types, in breast cancer progression and therapy response.

In the first part of my thesis, I describe how macrophages can acquire different functional characteristics in different types of breast cancer. Next, I focused on understanding the interplay between macrophages and cancer therapies. In particular, I revealed that macrophages counteract the efficacy of conventional chemotherapy drugs. I showed that eliminating macrophages with an antibody that targets CSF-1 receptor (CSF-1R) enhances the anti-cancer efficacy of platinum-based chemotherapeutic agents in breast cancer. I mechanistically discovered that CSF-1R inhibition stimulates intratumoral type I interferon signaling which is essential for the therapeutic synergy between cisplatin and CSF-1R blockade. I also uncovered that further elimination of immunosuppressive neutrophils, another type of immune cells, was required to engage an efficacious anti-tumor immunity.