Impact of early molecular changes in innate immune cells associated with human glioma progression

Abstract

Diffuse gliomas are primary brain tumors characterized by infiltrative growth and high heterogeneity, which render the disease mostly incurable. Advances in genetic analysis revealed that molecular and epigenetic alterations predict patients' overall survival and clinical outcome. However, glioma tumorigenicity is not exclusively caused by its genetic alterations. The crosstalk between tumor cells and the surrounding microenvironment plays a crucial role in modulating glioma growth and aggressiveness. The most abundant non-neoplastic cells in this microenvironment belong to the myeloid lineage, comprising CNS-resident microglia and infiltrating bone marrow-derived monocytes/macrophages. Understanding the dynamics between tumor and myeloid cells and the correlation between oncogenic molecular alterations in the tumor and the early changes leading to pro-tumorigenic activation of innate immunity cells would elucidate potential treatment alternatives.This is a collaborative study between the University of Groningen, Michigan University and the University of São Paulo, which includes a technology transfer agreement between the three universities. Other institutions participating in this project are Sírio Libanês Research and Educational Institute and the Neurosurgery Department of Sírio Libanês Hospital. This study is a continuation of the research initiated in 2013 (#2013/07704-3 and #2013/06315-3), which resulted in two publications (one accepted by "Methods in Molecular Biology" and a second manuscript currently under revision with "Nature Neuroscience"), with data still in preparation for additional two publications. We are applying this project to FAPESP as a Post Doctorate proposal.