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Reprogramming immune cells and molecules to counteract tumours that are able to evade the immune system is an approach that we are only starting to see the full potential of as a therapeutic tool. Successful reprogramming that safely and specifically targets cancer cells requires a detailed understanding of how these molecules and cells operate in the context of the tissue microenvironment in both health and disease. Research seeking to understand this will lead to new approaches and therapeutic combinations required for developing new cancer cures.