Genetic manipulation and genetic-based dissection of tumor-specific immunity

Mezzadra, R. (2019)

Doctoral Thesis

In this thesis I have firstly applied gene transfer technologies to the redirection of T cell specificity, by trying to overcome limitations related to non-viral gene transfer systems. In the second part of my PhD work, I focused on genetic screens, which, I applied to understanding molecular mechanisms of escape from T cell attack and to reveal mechanisms of PD-L1 regulation.
The work presented in this thesis may on the one hand facilitate the clinical application of non-viral-based gene transfer systems in T cells. On the other hand, the more fundamental discoveries related to IFN-γ-mediated tumor cell killing and PD-L1 regulation may help to further understand resistance toward immunotherapies and how to overcome them.

• PD-L1
• T cells
• genetic screens
• transposon-mediated gene-transfer
• SLFN11
• IFN-gamma
• TCR

• All authors: Mezzadra, R.
• Supervisor: Schumacher, A.N.M.
• Co-supervisor: Peeper, D.S.
• Committee: Haanen, J.B.A.G.; Borst, J.; Neefjes, J.; Brummelkamp, T.R.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2019-02-19
• ISBN (print): 9789463801867