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10 Headlines KILLING THE KILLERS Harnessing the power of our own immune system G lioblastoma multiforme, or GBM, is an aggressive type of brain cancer that grows very quickly with devastating results. Sadly, most patients survive less than a year after diagnosis. GBM cells are remarkably good at tricking a patient’s immune system into thinking they’re normal, thus evading attack. So how do you find – and kill – a killer that’s hiding in plain sight? Despite plenty of international research, that question has so far eluded experts. Now, groundbreaking research at the University of Auckland has shed light on why clinical trials haven’t worked so far – and identified a plan of attack that holds great promise. GBM is a cold tumour. Cold tumours are surrounded by cells that can suppress the immune response and keep T cells (a type of immune cell) from attacking and killing them. Associate Professor Scott Graham, who is head of the university’s NeuroImmune Interactions Research Group, has been looking closely at GBM since being funded by the Neurological Foundation in 2016. “Normally we have an immune response that recognises cells that are dead and dying, and removes them,” says Dr Graham. “But these tumour cells are pretending to be perfectly normal – they are hiding in plain sight.” Not only do they evade detection, they also switch off the body’s immune system – something that became apparent as Dr Graham and his team looked more closely. “It’s even worse than we expected – which makes sense, because otherwise the treatments would have worked when it was hypothesised that patients would do much better.” For example, CHECKMATE trials in the US using new-generation blockbuster monoclonal antibody therapies failed to increase survival in GBM patients. Dr Graham says, “While T cells (which are antigen-specific) have killing ability, GBM cells can inhibit them or ‘switch them off’. Simply blocking one or two pathways is not enough, because the GBM cells can suppress the T cells through different pathways.” So a new approach is needed. Enter natural killer cells – immune cells that are regulated in slightly different ways. They’re very good at detecting infection but also have natural ability to detect and kill cancer. Natural killer cells patrol the body reading cell surfaces, looking for a series of molecules confirming each cell is healthy. During a viral infection or when a cell becomes cancerous, those molecules change and are lost. “Natural killer cells recognise these changes and interrogate whether the target cells should be killed,” says Dr Graham. “If the GBM cell ‘looks’ like a normal, healthy cell, it will be left alone. So, we need to uncloak the GBM cells so they’re