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

Pigment Cell Melanoma Res. 2021 Sep;34(5):978-983. doi: 10.1111/pcmr.12958. Epub 2021 Jan 24.

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.

Keywords: Melanoma; biomarkers; germline variants; immune checkpoint inhibitors.

Publication types

  • Clinical Trial
  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Exome Sequencing
  • Exons*
  • Female
  • Germ-Line Mutation*
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage*
  • Male
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / pathology
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Receptors, Interleukin-1 Type I / genetics*

Substances

  • IL1R1 protein, human
  • Immune Checkpoint Inhibitors
  • Neoplasm Proteins
  • Receptors, Interleukin-1 Type I