Investigating the molecular mechanisms of microenvironment-dependent immune escape to natural killer cells in myeloma to uncover biomarkers for rational combination treatment strategie

Description

The research project aims to understand the molecular mechanisms behind microenvironment-dependent immune escape to natural killer (NK) cells in myeloma, with the goal of identifying biomarkers for rational combination treatment strategies. Aim 1 involves validating candidate markers of NK cell resistance and investigating NK cell adaptive changes in primary myeloma samples at different disease stages using data from CRISPR screens and single-cell RNA sequencing. Aim 2 focuses on exploring the crosstalk between myeloma cells and macrophages and its impact on NK cell activation and migration, particularly in the context of monoclonal antibodies. Functional assays, RNA sequencing of the secretome, and a novel in vitro NK cell migration assay using a microfluidic MM model will be employed to elucidate the complex interactions within the myeloma microenvironment and identify potential therapeutic targets.