The impact of one: single cell analysis of T cell states in human cancer

Leun, A.M. van der (2022)

Doctoral Thesis

Immune checkpoint therapies that aim to (re)activate the immune response against cancer cells have shown promising results in a variety of tumor types. Yet, a large fraction of cancer patients does not benefit from these therapies. While the presence of a substantial number of immune cells, and in particular T cells, in the tumor is generally related with a better clinical response to checkpoint therapies, the T cells in the tumor are diverse in their capacity to eliminate the tumor. In order to improve treatment outcome of cancer patients, we require a better understanding of the roles of different T cells in the response (and resistance) to immune checkpoint therapy. The development of single cell profiling technologies has provided us with a powerful tool to analyze the state and functionality of individual cells. In this thesis, I have used single cell profiling methods in combination with innovative experimental technologies to unravel the diversity of T cells in human tumors and define the changes in the profiles of T cells that occur in response to treatment with immune checkpoint therapy to dissect which T cells are important for therapy response.

• Tumor immunology
• T cells
• Cancer
• Immune checkpoint blockade
• Single cell sequencing
• Transcriptome analysis

• All authors: Leun, A.M. van der
• Supervisor: Schumacher, A.N.M.
• Co-supervisor: Thommen, D.S.
• Committee: Amit, I.; Visser, K.E. de; Haanen, J.B.A.G.; Zuur, C.L.; Van Steensel, B.; Akkari, L.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2022-11-22
• ISBN (print): 9789464195965