Germline variants in exonic regions have limited impact on immune checkpoint blockade clinical outcomes in advanced melanoma.
Melanoma
biomarkers
germline variants
immune checkpoint inhibitors
Journal
Pigment cell & melanoma research
ISSN: 1755-148X
Titre abrégé: Pigment Cell Melanoma Res
Pays: England
ID NLM: 101318927
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
11
12
2020
received:
20
08
2020
accepted:
10
01
2021
pubmed:
16
1
2021
medline:
5
2
2022
entrez:
15
1
2021
Statut:
ppublish
Résumé
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.
Substances chimiques
IL1R1 protein, human
0
Immune Checkpoint Inhibitors
0
Neoplasm Proteins
0
Receptors, Interleukin-1 Type I
0
Types de publication
Clinical Trial
Letter
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
978-983Informations de copyright
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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