Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma

Melanoma is a lethal form of skin cancer. Immunotherapeutic agents such as anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) have revolutionized melanoma treatment; however, drug resistance is rapidly acquired. Several studies have reported an increase in melanoma rates in older patients. Thus, the impact of ageing on transcriptional profiles of melanoma and response to immunotherapy is essential to understand. In this study, the bioinformatic analysis of RNA seq data of old and young melanoma patients receiving immunotherapy identifies the significant upregulation of extra-cellular matrix and cellular adhesion genes in young cohorts, while genes involved in cell proliferation, inflammation, non-canonical Wnt signaling and tyrosine kinase receptor ROR2 are significantly upregulated in the old cohort. Several Treg signature genes as well as transcription factors that are associated with dysfunctional T cell tumor infiltration are differentially expressed. The differential expression of several genes involved in oxidative phosphorylation, glycolysis and glutamine metabolism is also observed. Taken together, this study provides novel findings on the impact of ageing on transcriptional changes in melanoma, and novel therapeutic targets for future studies.