Germline variants in exonic regions have limited impact on immune checkpoint blockade clinical outcomes in advanced melanoma

Abstract

Immune checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however, up to 60% of treated patients do not respond to ICI and/or develop immune-related adverse events (irAEs). Currently, robust and reliable biomarker to predict response and/or occurrence of irAEs to ICI are missing. Herein, we wanted to explore whether germline variants (SNPs) could predict the clinical outcomes of melanoma patients treated with ICIs. We performed a whole exome sequencing using gDNA isolated from blood, from a discovery cohort of 57 patients with metastatic melanoma. The top associations were then tested in a validation cohort of 57 patients. Our work suggests that individual germline genetic variants have no or weak impact on the response to ICIs. Only, variants in IL1RL1 have a significant impact in treatment response. The role of IL1RL1 in the immune response against melanoma and as a theranostic marker warrants further investigations.