PO-414 Stage IV melanoma patients with tumoural MHC class i loss only respond to anti-PD-1 therapy in the presence of high NK cell density

Introduction Prior to 2011 there were no effective systemic therapies for advanced stage melanoma patients and the overall survival was 7.5 months. Recently, immune checkpoint inhibitors, anti-PD-1 and anti-CTLA-4 inhibitors, have produced response rates as high as 50% and doubled overall survival, but only 30% of patients have a durable response. One important resistance mechanism to immunotherapies is the downregulation of MHC Class I, resulting in the expansion of melanoma cells resistant to CD8 +T cell killing. Natural Killer (NK) cells monitor MHC Class I expression and eliminate cells that fail to express it; thus, NK cells are likely critical in preventing resistance to anti-PD-1 therapy. This study sought to investigate whether tumour-infiltrating NK cells in the presence of MHC class I loss improved survival outcome of patients treated with anti-PD-1. Material and methods Twenty-five stage IV metastatic melanoma patients treated with anti-PD-1 therapy were categorised into responders (CR/PR/SD >6 mo, n=13) and non-responders (SD Results and discussions Differential expression analysis identified nine up-regulated NK cell specific genes in responders when compared to non-responders (adjusted p Conclusion This study showed that the presence of higher numbers of NK cells are associated with improved responses to anti-PD-1 therapy. Most importantly, responding patients with MHC class I loss had higher NK cell densities, suggesting that NK cells play an important role in mediating response to anti-PD-1 in patients whose tumour down regulates MHC class I expression.