Abstract

3D Hydrogel as Clinically-Relevant Neuroblastoma Model Where to Test Novel Antibody-Mediated Therapies

silvia scaglione, Researcher and team leader, CNR

Currently, treatment failures of neuroblastoma (NB) may be due to the lack of reliable in vitro models for establishing the efficacy of potential therapeutics. We here propose 3D alginate-based hydrogels as extracellular tumor microenvironment with the aim to evaluate the effects of the three-dimensionality on a plethora of ligands regulating the immune response. This analysis highlighted a novel and clinical-relevant NB immunophenotype. In particular, among others, we analyzed a ligand (PVR), involved in the formation of immune synapses during Natural killer (NK) cells /target interactions and that is crucial for killing of ex-vivo derived tumors. Interestingly, the PVR trend observed in our 3D model in presence of a soluble factor (IFN-gamma), released by NK cells during immune response, well resemble the PVR variations occurring in vivo, which, on contrary, are not well appreciated in 2D standard culture conditions. Therefore, the here proposed NB cell-laden alginate hydrogels might represent a pre-clinical culture system where to test the recent therapeutic approaches aimed to target PVR, which appears to be highly and, quite selectively, expressed by several tumor histotypes.