Germline variants in exonic regions have limited impact on immune checkpoint blockade clinical outcomes in advanced melanoma. (24th January 2021)

• Record Type: Journal Article
• Authors: Montaudié, Henri; Beranger, Guillaume Emmanuel; Reinier, Frédéric; Nottet, Nicolas; Martin, Hélène; Picard‐Gauci, Alexandra; Troin, Laura; Ballotti, Robert; Passeron, Thierry
• Is Part Of: Pigment cell & melanoma research. Volume 34:Number 5(2021)
• Page Start: 978
• Page End: 983
• Publication Date: 2021-01-24
• Subjects: biomarkers -- germline variants -- immune checkpoint inhibitors -- Melanoma; Melanoma -- Periodicals; Chromatophores -- Periodicals; Animal pigments -- Periodicals; 616.99477
• DOI: 10.1111/pcmr.12958
• Languages: English
• ISSNs: 1755-1471

Abstract

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.