Autoimmune genetic risk variants as germline biomarkers of response to melanoma immune-checkpoint inhibition. Academic Article uri icon

Overview

abstract

  • Immune-checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however, > 60% of treated patients do not respond to ICI. Current biomarkers do not reliably explain ICI resistance. Given the link between ICI and autoimmunity, we investigated if genetic susceptibility to autoimmunity modulates ICI efficacy. In 436 patients with metastatic melanoma receiving single line ICI or combination treatment, we tested 25 SNPs, associated with > 2 autoimmune diseases in recent genome-wide association studies, for modulation of ICI efficacy. We found that rs17388568-a risk variant for allergy, colitis and type 1 diabetes-was associated with increased anti-PD-1 response, with significance surpassing multiple testing adjustments (OR 0.26; 95% CI 0.12-0.53; p = 0.0002). This variant maps to a locus of established immune-related genes: IL2 and IL21. Our study provides first evidence that autoimmune genetic susceptibility may modulate ICI efficacy, suggesting that systematic testing of autoimmune risk loci could reveal personalized biomarkers of ICI response.

publication date

  • March 12, 2019

Research

keywords

  • Autoimmune Diseases
  • Biomarkers, Tumor
  • Genetic Predisposition to Disease
  • Immunotherapy
  • Melanoma

Identity

PubMed Central ID

  • PMC6531317

Scopus Document Identifier

  • 85063014451

Digital Object Identifier (DOI)

  • 10.1016/S1470-2045(15)70076-8

PubMed ID

  • 30863922

Additional Document Info

volume

  • 68

issue

  • 6