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12.03.2019 | Original Article

Autoimmune genetic risk variants as germline biomarkers of response to melanoma immune-checkpoint inhibition

verfasst von: Vylyny Chat, Robert Ferguson, Danny Simpson, Esther Kazlow, Rebecca Lax, Una Moran, Anna Pavlick, Dennie Frederick, Genevieve Boland, Ryan Sullivan, Antoni Ribas, Keith Flaherty, Iman Osman, Jeffrey Weber, Tomas Kirchhoff

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2019

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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.

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Titel: Autoimmune genetic risk variants as germline biomarkers of response to melanoma immune-checkpoint inhibition
verfasst von: Vylyny Chat
Robert Ferguson
Danny Simpson
Esther Kazlow
Rebecca Lax
Una Moran
Anna Pavlick
Dennie Frederick
Genevieve Boland
Ryan Sullivan
Antoni Ribas
Keith Flaherty
Iman Osman
Jeffrey Weber
Tomas Kirchhoff
Publikationsdatum: 12.03.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 6/2019
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02318-8

Springer Medizin

Autoimmune genetic risk variants as germline biomarkers of response to melanoma immune-checkpoint inhibition

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

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ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

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