Fair skinned individuals of 80 years and older in countries with high sun exposure have a skin cancer incidence of almost 100%, which is why this is the most expensive cancer to manage in Australia. The body’s immune system can eliminate most sun-damaged skin cells before they become cancer cells, but the mechanism behind this defence, or why it sometimes fails, is unknown. Gaining a better understanding of the interaction of damaged skin cells with the surrounding immune cells is crucial to develop immune treatments to overcome the problem, and these treatments. Commonly used mouse models of skin cancer do not address this problem well, due to the discrepancies between human and mouse skin, creating a demand for good human models to study skin cancer progression. In this project, we will use patient biopsies from sun-damaged skin, early lesions and fully developed skin cancer from individuals with intact immune system, or suppressed immunity after organ transplantation, to establish a human skin cancer progression model. With this model, we can study differences in sun-damaged skin cells that allow them to evade destruction by the immune system. Our findings will be an important step towards developing therapies that enhance patient’s immune response against skin cancer.