期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 68, 期 6, 页码 897-905出版社
SPRINGER
DOI: 10.1007/s00262-019-02318-8
关键词
Autoimmunity; Germline variants; Immune-checkpoint inhibition; Melanoma
资金
- National Cancer Institute [1R21CA184432-01]
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 rs17388568a risk variant for allergy, colitis and type 1 diabeteswas 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.
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