Germline variants in exonic regions have limited impact on immune checkpoint blockade clinical outcomes in advanced melanoma
| Autor: | Frederic Reinier, Hélène Martin, Thierry Passeron, Henri Montaudié, Guillaume E. Beranger, Alexandra Picard-Gauci, Robert Ballotti, Laura Troin, Nicolas Nottet |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty business.industry Melanoma Single-nucleotide polymorphism Dermatology medicine.disease General Biochemistry Genetics and Molecular Biology Immune checkpoint Germline 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immune system 030220 oncology & carcinogenesis Internal medicine Cohort Medicine Biomarker (medicine) business Exome sequencing |
| Zdroj: | Pigment Cell & Melanoma Research. 34:978-983 |
| ISSN: | 1755-148X 1755-1471 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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