Immune-checkpoint therapy in non-small cell lung carcinoma:molecular characterisation of tumour microenvironment to improve anti-PD1/PD-L1 drug class.

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Lung cancer kills more people worldwide than any other cancer and has already spread in most patients at diagnosis, for whom chemotherapy of limited effectiveness has been the only treatment available. Fortunately, a new class of 'immune modulating drugs' has been recently developed. These work by removing the defences the tumour develops to protect it from the body's normal immune system, exposing it to attack by the body's immune cells.The only means currently to predict whether these drugs will work is to assess the amount of a protein called PD-L1 on the tumour cells. Unfortunately, this particular 'biomarker' lacks accuracy; some patients who should respond do not and some patients who have little/no PD-L1 would probably respond but are missing out on this treatment. Our study will examine why PD-L1 lacks precision by looking at how it varies between different parts of the tumour and areas of tumour spread, how it relates to inflammation and genetic mutations, and how all of these inter-relate. Ultimately, we wish to improve the accuracy of determining whether an individual patient with lung cancer will respond to these drugs, so that the most beneficial treatment can be given in an efficient and cost-effective manner.