Characterization of tumor-associated microglia/macrophages in Glioblastoma and setting up of a large-scale drug screening for their functional reprogramming towards anti-tumoral cells
Glioblastoma (GBM) is the most aggressive and malignant tumor that afflicts the central nervous system. GBM microenvironment is populated by different cell types, with tumor-associated microglia/macrophages (TAMs) representing the most abundant non-neoplastic cells. TAMs make up a heterogeneous population displaying both pro- and anti-tumoral features. The ratio of these cells in the tumor microenvironment (TME) is linked with prognosis. For example, patients with high fractions of monocytes and monocyte-derived macrophages in the TME show reduced overall survival. In this context, several novel therapeutic strategies that target TAMs have been developed, mainly finalized to their depletion. Here, we aim to conduct a comprehensive characterization of the myeloid compartment in the TME and in the blood at the transcriptional and functional level to reprogram TAMs towards anti-tumoral cells. To achieve this ultimate goal, we use a combination of single-cell RNA-sequencing and functional assays as well as currently setting up a large-scale drug screening to identify molecules and pathways skewing specific TAM populations into cells displaying anti-tumoral activities.