biostudies-literatureTomlins SANCI NIH HHS14https://www.ebi.ac.uk/biostudies/studies/S-EPMC9905474biostudies-literatureUnknown3(1)<h4>Background</h4>Anti-PD-1 and PD-L1 (collectively PD-[L]1) therapies are approved for many advanced solid tumors. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability, and tumor mutation burden (TMB) may improve benefit prediction.<h4>Methods</h4>Using treatment data and genomic and transcriptomic tumor tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit. IRS real-world progression free survival (rwPFS) and overall survival (OS) prediction was validated in an independent cohort of trial patients.<h4>Results</h4>Here, by Cox modeling, we develop IRS-which combines TMB with CD274, PDCD1, ADAM12 and TOP2A quantitative expression-to predict pembrolizumab rwPFS (648 paCommunications medicineDevelopment and validation of an integrative pan-solid tumor predictor of PD-1/PD-L1 blockade benefit.PMC9905474P30 CA086862Burkard MEYang ESDees ECTomlins SAParsons BNair SSlim JNHu-Seliger TKhatri JHovelson DHMasters GHipp JSiegel RThomas SRhodes DREdenfield WJMenter AKhazanov NAMitchell KDrewery SLamb LEMiller AMSuga JMMisleh JPlouffe KReeder TJohnson DBOnitilo AAShreve MJHwang LCWassenaar TFischer ABulen BJThompson MIrvin WMatrana MRVakil HBuchschacher GLKwiatkowski KSafa MCzuprenski EAnderson DMfalseDevelopment and validation of an integrative pan-solid tumor predictor of PD-1/PD-L1 blockade benefit.<h4>Background</h4>Anti-PD-1 and PD-L1 (collectively PD-[L]1) therapies are approved for many advanced solid tumors. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability, and tumor mutation burden (TMB) may improve benefit prediction.<h4>Methods</h4>Using treatment data and genomic and transcriptomic tumor tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit. IRS real-world progression free survival (rwPFS) and overall survival (OS) prediction was validated in an independent cohort of trial patients.<h4>Results</h4>Here, by Cox modeling, we develop IRS-which combines TMB with CD274, PDCD1, ADAM12 and TOP2A quantitative expression-to predict pembrolizumab rwPFS (648 pa2023-01-01T00:00:00Z2023 Feb2026-05-28T12:46:53.956Z2025-04-05T19:41:40.237ZS-EPMC99054743675061710.1038/s43856-023-00243-7