Exploring and exploiting cell cycle regulation of CD8+ T cells

Haften, F.J. van (2025)

Doctoral Thesis

Cancer is the second leading cause of death worldwide. Cancer patients are treated with distinct therapies, including radiotherapy, immunotherapy, and chemotherapy of which the latter is being given to 30% of cancer patients. These chemotherapeutic drugs are designed to target rapidly proliferating cancer cells and thereby induce tumor cell killing. While the effects of chemotherapy on cancer cells are well-studied, the effects on other proliferating cells, including immune cells like cytotoxic CD8+ T cells, which have the ability to directly eliminate tumor cells, are not well known yet. Given the importance of CD8+ T cells in the fight against cancer, it is essential that we better understand the effects of chemotherapy on CD8+ T cells.
In this thesis we show the effects of short-term cell cycle inhibition on CD8+ T cell proliferation, with a specific focus on the metabolism. We show and discuss how our findings on CD8+ T cell proliferation can contribute to improving T-cell based therapies in the clinic. Furthermore, we give suggestions on how to accomplish this and how future research can contribute to further improve immunotherapy for cancer patients.

• Immunology
• CD8+ T cells
• Tumors
• Cell cycle regulation
• Metabolism
• Immunotherapy
• Chemotherapy
• In vivo studies

• All authors: Haften, F.J. van
• Supervisor: Arens, R.; Neefjes, J.J.C.
• Committee: Heemskerk, M.H.M.; Amsen, D.; Danmeijer, F.; Salerno, F.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2025-10-30