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Germline variants in exonic regions have limited impact on immune checkpoint blockade clinical outcomes in advanced melanoma
Author(s) -
Montaudié Henri,
Beranger Guillaume Emmanuel,
Reinier Frédéric,
Nottet Nicolas,
Martin Hélène,
PicardGauci Alexandra,
Troin Laura,
Ballotti Robert,
Passeron Thierry
Publication year - 2021
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12958
Subject(s) - medicine , exome sequencing , melanoma , germline , immune checkpoint , exome , oncology , blockade , cohort , immune system , adverse effect , biomarker , immunotherapy , immunology , cancer research , mutation , biology , genetics , gene , receptor
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.