The aim of this project is to establish the foundation for advanced molecular analyses that will elucidate mechanisms underlying glioblastoma resistance and response to immunotherapy, identify predictive biomarkers, and support the development of innovative, patient-tailored therapeutic strategies for GB treatment.
Specific objectives of the project are:
Objective 1: To explore the response of GB to NK cell-based treatment with the agonist IL-15 (N-803) and TGF-β inhibitor galunisertib in a clinically relevant GB organoid model.
Objective 2: To investigate the resistance mechanisms and the composition of TME in a spatial context. We will focus on GB stem cell (GSC) niches, which influence the response to NK cell-based therapy combined with the TGF-β inhibitor galunisertib. This will be achieved through spatially resolved transcriptomic profiling of GBOs using In Situ Sequencing (ISS) in responders and non-responders.
Project will be implemented in 4 work packages:
Fig. 2 Scheme representing the Work Packages (WPs) of the TRUST-NK project. This figure illustrates the structure and flow of the project, organized into distinct work packages (WPs).