UCL Cancer Institute Special Seminar

Glioblastoma multiform (GBM) is the most common and deadly form of brain cancer. Despite intensive research the median survival of GBM remains at 1 year, with less than 10 % of patients surviving over 5 years. Previously, we identified MerTK, SYK and LYN were overexpressed in GBM by glioma cells, and we demonstrated that they play a critical function in GBM malignancy. Interestingly, these kinases are closely related to the immune system. MerTK is a well-known macrophage receptor involved in phagocytosis and SYK (and Zap70) are downstream of over 90 immune molecules (including TCR, BCR and Fc receptors) through their immunoreceptor tyrosine-based activation motifs (ITAMs). 

We have found that “Immune system process” was the Gene Ontology (GO) term ranked first, according to lowest P-value in three GBM datasets and that although the enrichment for GO terms associated with immune system processes seemed unsurprising at first, we could confirm that a range of GBM cell lines expressed immune cell markers.   We also found that the expression of ITAM bearing molecules, such as Fc receptors, T cell receptor components and C-type lectins, was up regulated within two distinct tumour-derived prognostic signatures identified in GBM and low-grade gliomas. Targeting SYK attenuated GBM tumour growth and invasiveness, and reduced B and CD11b+ cell mobility and infiltration resulting in improved survival. Our data shows that gliomas are hematopoietic-like tumours that express an immune signalling network essential to glioma genesis and progression, and identify targets for therapeutic intervention. We are now also investigating whether expression of hematopoietic ITAM molecules is a specific property of human gliomas or whether this represents a more general feature of invasive cancers.

Hosted by Dr Simone Ecker

For further information contact: Veronica Dominguez v.dominguez@ucl.ac.uk

Location

UCL Cancer Institute
Courtyard Café
72 Huntley Street
London, WC1E 6DDView Map