A game of hide and seek: targeting neuroblastoma’s escape from immunotherapy

This highly translational project specifically addresses the clinical problem that in ca 50% of patients, neuroblastoma tumors evade the current immunotherapy with anti-GD2. Most of these patients don’t survive, and currently we cannot predict which patients will respond to anti-GD2. This project will focus on identifying treatments that can either undermine tumor immune evasion or increase the anti-tumor activity of immune cells.

I will use advanced techniques including high-throughput drug screening and CRISPR screening of neuroblastoma for anti-GD2 resistance to identify novel combination strategies. Moreover, I will study the effect of ex vivo anti-GD2 treatment on activation and remodeling of the tumor immune environment on primary tumor fragments, and I will explore whether these ex vivo responses can predict clinical responses in patients. The identified promising combination strategies will be validated in vitro and in vivo using our available neuroblastoma models (e.g. organoids, mouse models) with the goal of translating them into the clinical setting. Lastly, part of this project will be a data-oriented systematic literature review of candidate immunotherapy targets with the highest potential for clinical translation.

Beatrice Piotto