Understanding the biological mechanisms leading to poor outcome in melanoma of the elderly population and developing secondary prevention strategies (360G-Wellcome-110078_Z_15_Z)

Incidence and mortality rates in melanoma are highest in the elderly. Age is an independent adverse prognostic factor. Even when old and young patients present matched prognostic criteria, old patients are less likely to survive. This project will identify the mechanism(s) underlying poor melanoma survival in the elderly; and will develop melanoma progression prevention strategies. 1)We will study if the elderly are more vulnerable to melanoma; testing whether skin of mice/humans presents an a ltered inflammatory response to ultraviolet radiation(UVR); whether old skin is less able to repair UVR-induced DNA damage; and if aged cells in the microenvironment contribute to melanomagenesis. 2)We will investigate if tumours in the elderly are inherently more aggressive by integrating salient epidemiological, clinical data with immunological and genetic criteria from 400 young/old high-risk melanoma patients with favourable/unfavourable prognosis. We will overlay deep-targeted sequencing of genes driving progression and the patterns of interaction of neutrophils, macrophages, dendritic cells and lymphocytes in the tissue of high-risk patients to investigate host response in young and old patients. This will reveal prognostic categories integrating multidisciplinary data points and will inform biology. C)We will test adjuvant rationales to prevent melanoma progression in the elderly at high risk of death.