Immune cell complexity in the tumor microenvironment of breast cancer

Salvagno, C. (2019)

Doctoral Thesis

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.

• Tumor-associated macrophages
• Chemotherapy
• Breast cancer
• Neutrophils

• All authors: Salvagno, C.
• Supervisor: Visser, K.E. de
• Co-supervisor: Coffelt, S.B.
• Committee: Borst, J.; Jonkers, J.; Rheenen, J. van; Burg, S.H. van den
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2019-10-22
• ISBN (print): 9789463804394