The Role of Physical Membrane Properties in Tumour Cell Resistance to Perforin

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To kill virus-infected and cancer cells, the human immune system can use white blood cells that expose their targets to a mixture of toxic proteins. This is exploited by so-called cancer immunotherapies, which induce the immune system to more effectively target tumours. However, the success of these therapies strongly depends on the type of cancer and can be remarkably variable - even for the same type of cancer - from one patient to the other, for reasons that remain poorly understood.In the mix of proteins secreted by these white blood cells, an essential protein is perforin, which punches holes in the target cells. We have only recently discovered how the white blood cells are protected against the perforin they secrete, preventing them from being damaged every time they kill a target (e.g., a cancer cell). This protection resides in the physical properties of the membrane that surrounds the white blood cells, in particular in how the fatty acid molecules ("lipids") in the membrane are packed and what electric charge they have at the membrane surface.With this project, we aim to investigate if a similar protection may be used by cancer cells, to protect them against perforin and to thus reduce the efficiency at which they are cleared by the immune system. If this is the case, this can be used as an inspiration for strategies that enhance the efficacy of cancer immunotherapies and/or as a way to test patient resistance to such therapies before they are treated.