Systemic immune dynamics in cancer

Bakker, E.A.M. (2026)

Doctoral Thesis

Breast cancer is the most common cancer in women and a major cause of mortality. The immune system plays a crucial role in recognizing and combating tumors, but in breast cancer this role is complex and varies greatly by disease subtype and stage. In my research, I investigated how the immune system changes in breast cancer and how this knowledge may contribute to improved understanding and treatment of the disease.

Through extensive analyses of blood samples from patients with different forms of breast cancer, I found that the immune system becomes dysregulated in advanced disease. This was particularly evident in the aggressive triple-negative subtype (TNBC), where pronounced abnormalities were observed, especially in certain white blood cells such as neutrophils. In patients with metastatic TNBC, these cells were not only more abundant but also more active and functionally distinct compared with those in healthy individuals.

In addition, we studied how immunotherapy—a treatment that enhances the body’s own immune response—works in breast cancer. In patients with early-stage TNBC, a short course of immunotherapy before surgery could already induce strong immune activation and, in some cases, complete tumor disappearance. In metastatic TNBC, we identified another immune cell type, the eosinophil, as important for a favorable response to immunotherapy.

These findings provide new insight into the interaction between breast cancer and the immune system and may contribute to more targeted, effective, and less burdensome treatments for patients.

• Innate
• Adaptive
• Immune System
• Breast Cancer
• uVIN
• Vaccination
• Her2
• HR
• TNBC
• Neutrophil
• Cell migration
• ROS
• Clinical trials
• Immunotherapy
• Biomarker discovery

• All authors: Bakker, E.A.M.
• Supervisor: Visser, K.E. de
• Co-supervisor: Kok, M.
• Committee: Portielje, J.E.A.; Heemskerk, M.H.M.; Arens, R.; Jacobs, H.; Ven-van Balken, R. van de
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2026-01-09