Germline genetic host factors as predictive biomarkers in immuno-oncology  Vylyny Chat, Robert Ferguson, Tomas Kirchhoff  Immuno-Oncology Technology  Volume 2, Pages 14-21 (September 2019) DOI: 10.1016/j.iotech.2019.08.001 Copyright © 2019 Terms and Conditions

Figure 1 Proposed strategies for the discovery, validation and clinical implementation of germline genetic biomarkers of immune-checkpoint inhibition (ICI) outcomes. A genome-wide analysis in the setting of a large collaborative consortium that pools patients' resources and harmonized clinical information identifies ICI-associated germline variation using genome-wide association studies, whole-genome sequencing or whole-exome sequencing platforms. Multi-omic data are integrated to further refine and prioritize genomic loci for targeted validation in an independent patient cohort. Functional and clinical validation is performed on a subset of germline variants that are reproducibly associated with ICI clinical outcomes in both discovery and validation patient cohorts. The validated host germline genetic markers can subsequently be integrated with other ICI biomarkers to generate personalized ICI prediction models (cancer immunograms). Further clinical tests in prospective populations can be designed (likely in the framework of a prospective clinical trial) to translate the germline genetic biomarkers of immuno-oncology outcomes into routine clinical practice following the biomarker development pipelines established previously [115,116]. Immuno-Oncology Technology 2019 2, 14-21DOI: (10.1016/j.iotech.2019.08.001) Copyright © 2019 Terms and Conditions