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

Abstract

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.