Brain tumours take control of sugar metabolism to grow: Study

Immune cells within a brain tumour could be taking control of sugar metabolism breaking down fructose to suppress immune responses and promote tumour growth a study has foundPublished in the journal Proceedings of the National Academy of Sciences the study is the first to identify a sugar metabolism driving immune suppression in glioblastoma an aggressive rapidly growing malignant tumour in the brain researchers saidThey suggested blocking how fructose gets broken down in specialised immune cells may improve a patients response to immunotherapy and outcomesAcross several mouse models when we removed the fructose transporter the tumours simply didnt grow senior author Jason Miska assistant professor of neurological surgery at Northwestern Universitys school of medicine saidGlioblastoma is among the most treatmentresistant brain tumours partly because of its tumour microenvironment or the mix of cells surrounding the tumour including microgliaMicroglia are immune cells that surround and support neurons nerve cells in the central nervous system Crucial for the early stages of tumour growth microglia also express a unique fructose transporter GLUT5 enabling them to transport and metabolise the sugar moleculeVaried analytical techniques including genetic sequencing methods were used to study microglia macrophages which are immune cells that can enter tumours from the bloodstream and tumour cellsThe analysis confirmed that microglia uniquely express GLUT5 and showed microglia to be the only immune cells in the glioblastoma microenvironment capable of breaking down fructoseWe knew microglia use this fructose transporter as part of their normal biology but we did not expect it to be this important for brain tumour growth Miska saidIn mice genetically engineered without the GLUT5 transporter tumours were seen to produce a much stronger immune response including a better recognition of tumour cells an increased production of cytokines driving inflammation and a rapid multiplication of CD8 Tcells the immune systems main cancerkilling cellsThis not only makes the microglia themselves more inflammatory but it also causes those Tcells and Bcells that are in the tumour to be more activated and create more inflammatory molecules that we have shown are required for rejection of brain tumours first author Leah Billingham a postdoctoral fellow in Miskas lab saidThis isnt just solely the microglia doing something this is an intricate interaction between the different parts of the immune system and how they are then impacting tumour rejection Billingham saidMicroglial fructose metabolism is a key regulator of immune suppression in glioblastoma and may be a promising therapeutic target to improve immunotherapy response in patients the researchers suggestedThe authors demonstrate that microglia uniquely express the fructose transporter GLUT5 and are the only immune cells in the GBM glioblastoma microenvironment capable of metabolising fructoseThey show that a global deletion of GLUT5 confers profound resistance to tumour growth This effect is driven by loss of fructose metabolism in microglia and occurs independently of contributions from peripheral immune compartmentsThis story has been sourced from a third party syndicated feed agencies Midday accepts no responsibility or liability for its dependability trustworthiness reliability and data of the text Midday managementmiddaycom reserves the sole right to alter delete or remove without notice the content in its absolute discretion for any reason whatsoever