ImmunoGBMet · Understanding iNKT cell Metabolic features in GlioBlastoMa tumours to improve Immunotherapy

Glioblastoma (GBM) is one of the most aggressive and fatal types of tumours with one of the worse survival rates. Although immunotherapy is a remarkable and fast-growing field on cancer treatment it still faces the challenge that solid tumours are very suppressive for immune cells. This suppressive tumour microenvironment (TME) is known to affect immune cells in different ways, as through the expression of inhibitory ligands and cytokines. Recently, it has been shown that lipids and other metabolites are increased in the TME and affect metabolic pathways in immune cells leading to their dysfunction. NKT cells are a distinct subset of lymphocytes that react to lipids presented via the CD1d molecule and produce a range of cytokines upon activation. They play a role in tumoral immunity either through cytotoxicity or by activating other cytotoxic lymphocytes. However, little is known about their function in the GBM tumour and how the TME affects it. This project will leverage expertise in immunometabolism to describe the alterations in NKT cell metabolism that lead to their dysfunction in the GBM TME. We will take advantage of single-cell metabolic tools and proteomics analysis to unveil the most altered pathways, then, set up the best approaches to engineer NKT cells and make them resistant to the adverse TME. Our findings will potentially pave the way to new strategies on engineering immune cells for cancer immunotherapy and other serious conditions.