Activated microglia in human brain tumours – a translational study.

Gliomas are the most common type of intrinsic brain tumour and a major cause of morbidity and mortality for those afflicted by these highly invasive tumours. The majority of adult gliomas are high-grade astrocytomas comprising grade 3 anaplastic astrocytoma (AA) and grade 4 glioblastoma multiforme (GBM). Gliomas contain tumour cells as well as microglia, which are known to contribute to the tumour mass. Microglia are the immunocompetent cells of the central nervous system and could potentially promote tumour growth and invasion. Under normal conditions microglia assume a quiescent/resting (ramified) phenotype, but in the setting of brain tumours they become activated. Activated microglia are capable of releasing various immunomodulatory molecules (cytokines and chemokines) which could alter the course of tumourogenesis. In this study we will be recruiting patients undergoing surgery for removal of their tumour. The resected tumour will be cultured in the laboratory and the role of activated microglia in tumour proliferation will be examined. We will be looking at some of the cytokine and chemokine cascades in order to identify various key players in tumourogenesis. We will also be focusing on a specific receptor, P2X7R, found in microglia which has been implicated in tumour growth. The ultimate aim is identify pharmacological agents that can combat human brain tumours.