Autoimmune genetic risk variants as germline biomarkers of response to melanoma immune-checkpoint inhibition
| العنوان: | Autoimmune genetic risk variants as germline biomarkers of response to melanoma immune-checkpoint inhibition |
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| المؤلفون: | Antoni Ribas, Genevieve M. Boland, Anna C. Pavlick, Danny Simpson, Jeffrey S. Weber, Dennie T. Frederick, Esther Kazlow, Rebecca Lax, Robert Ferguson, Tomas Kirchhoff, Vylyny Chat, Una Moran, Iman Osman, Keith T. Flaherty, Ryan J. Sullivan |
| المصدر: | Cancer Immunol Immunother Cancer immunology, immunotherapy : CII, vol 68, iss 6 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, Cancer Research, Programmed Cell Death 1 Receptor, Autoimmunity, Germline variants, medicine.disease_cause, Germline, 0302 clinical medicine, Risk Factors, Monoclonal, 80 and over, 2.1 Biological and endogenous factors, Immunology and Allergy, CTLA-4 Antigen, Aetiology, Melanoma, Immune-checkpoint inhibition, Cancer, Aged, 80 and over, screening and diagnosis, Tumor, Antibodies, Monoclonal, Single Nucleotide, Middle Aged, Detection, Oncology, Female, Immunotherapy, hormones, hormone substitutes, and hormone antagonists, Adult, Clinical Trials and Supportive Activities, Immunology, Single-nucleotide polymorphism, Autoimmune Disease, Polymorphism, Single Nucleotide, Antibodies, Article, Autoimmune Diseases, 03 medical and health sciences, Clinical Research, Genetics, Biomarkers, Tumor, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, Polymorphism, Colitis, Aged, Genetic association, business.industry, Prevention, Inflammatory and immune system, Interleukins, Human Genome, medicine.disease, Immune checkpoint, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, Germ Cells, Cancer research, Interleukin-2, business, Biomarkers, 030215 immunology |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1432-0851 0340-7004 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53c660af4373ce5847300e27d07688b2Test https://doi.org/10.1007/s00262-019-02318-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....53c660af4373ce5847300e27d07688b2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320851 03407004 |
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