Inter-patient and intra-tumoral heterogeneity in GBM is present at different levels - from histopathological appearance to genetic and molecular profiles. Heterogeneity plays an important role in tumor progression and treatment resistance. We have shown that phenotypic heterogeneity is shaped by the tumor microenvironment and interaction with surrounding brain parenchyma. Tremendous intrinsic plasticity permits GBM cells to switch between different phenotypes in a reversible manner. This property allows tumor cells to quickly adapt to changing microenvironments and escape therapeutic pressures.
Currently we examine tumor heterogeneity and long- and short-term resistance mechanisms at single cell -omic level to reveal specific phenotypic states responsible for adaptation to microenvironmental niches and resistance to treatment. This is combined with interrogating tumor microenvironment and interactions of tumor cells with non-malignant stroma upon resistance to treatment. We further explore the cross-talk between GBM cells and the specific immune components of the brain to design effective immunotherapies that will specifically target the unique brain tumor immune ecosystem.
This project is supported by the Luxembourg National Research Fund (I2TRON DTU), GLIOTRAIN ITN European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie (grant agreement No 766069) and Fondation du Pélican de Mie and Pierre Hippert-Faber.