Project Details
Projekt
Trained Spp1+ microglial immunity in glioma – (TRAINSPOTTING)
Applicant
Professor Dr. Michael Platten
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 500299701
Based on results from the first funding period substantiating the role of myeloid cells infiltrating gliomas in shaping not only T cell responses induced by vaccines or immune checkpoint inhibitors but also T cell-mediated glioma control by radiotherapy we hypothesize that trained immunity or innate immune memory are key mechanisms that orchestrates a long-lasting change in the immune microenvironment of gliomas with implications for the development of gliomas but also relapse after radiotherapy. In this project we will make use of the data, models and clinical trial samples generated and analyzed in the first funding period to unravel the molecular mechanisms involved in modulating innate immune memory in microglia cells with a specific focus on Spp1+ microglial cells, decipher the temporal and spatial dynamics and dissect the impact on glioma development and relapse after therapy. We will use established tools to induce innate immune memory and tolerance in microglial cells (WP1) and complement these studies with radiotherapy – a DNA damage inducing treatment modality for gliomas recently demonstrated to induce functionally relevant microglial innate immune memory (WP2). Finally, we will probe clinical trial samples to validate key molecular and cellular mechanisms identified in the preclinical models (WP3). We expect this dataset to provide important information guiding the development of rational combinatorial as well as novel Spp1+ microglia-targeting therapies for the prevention of recurrence and progression of glioma. In the framework of the SPP2395 we expect this dataset to provide important information on human microglial states but also states that are associated with priming, training and tolerance in health and disease.
DFG Programme
Priority Programmes
