A blood-based miRNA signature predicts immunotherapy efficacy in advanced stage non-small cell lung cancer
A blood-based miRNA signature predicts immunotherapy efficacy in advanced stage non-small cell lung cancer
Abstract Immunotherapies have recently gained traction as highly effective therapies in a subset of late-stage cancers. Unfortunately, only a minority of patients experience the remarkable benefits of immunotherapies, whilst others fail to respond or even come to harm through immune related adverse events. For immunotherapies within the PD-1/PD-L1 inhibitor class, patient stratification is currently performed using tumor (tissue-based) PD-L1 expression. However, PD-L1 is an accurate predictor of response in only ～30% of cases. There is pressing need for more accurate biomarkers for immunotherapy response prediction. We sought to identify peripheral blood biomarkers, predictive of response to immunotherapies against lung cancer, based on whole blood microRNA profiling. Using three well characterized cohorts consisting of a total of 334 stage IV NSCLC patients, we have defined a 5 microRNA risk score (miRisk) that is predictive of immunotherapy response in training and independent validation cohorts. We have traced the signature to a myeloid origin and performed miRNA target prediction to make a direct mechanistic link to the PD-L1 signalling pathway and PD-L1 itself. The miRisk score offers a potential blood-based companion diagnostic for immunotherapy that outperforms tissue-based PD-L1 staining.
Jehn Julia、Schenz Judith、Muley Thomas、Pelea Oana、Kahraman Mustafa、Heuvelman Marco、N?tzel Dennis、Tikk Kaja、Daniel-Moreno Alberto、Uhle Florian、Schindler Hannah、Wu Qianxin、Reck Martin、Hofmann Sarah、Mercaldo Nathaniel、Thomas Michael、Christopoulos Petros、Uhle Sandra、Feufel Jennifer、Skottke Jasmin、Ceiler Jessika、Sikosek Tobias、Lusky Fabienne、Sauka-Spengler Tatjana、Elshiaty Mariam、Kittner Paul、Weigand Markus A、Rabe Klaus F、Rajakumar Timothy、Ferry Quentin、Steinkraus Bruno R、Hinkfoth Franziska、Horos Rastislav
Hummingbird Diagnostics GmbHDepartment of Anesthesiology, Heidelberg University HospitalThoraxklinik and National Center for Tumor Diseases (NCT) at Heidelberg University HospitalMRC Weatherall Institute of Molecular Medicine, University of OxfordHummingbird Diagnostics GmbHHummingbird Diagnostics GmbHHummingbird Diagnostics GmbHHummingbird Diagnostics GmbHHummingbird Diagnostics GmbHDepartment of Anesthesiology, Heidelberg University HospitalThoraxklinik and National Center for Tumor Diseases (NCT) at Heidelberg University HospitalWellcome Sanger InstituteLungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung ResearchHummingbird Diagnostics GmbHInstitute for Technology Assessment, Department of Radiology, Massachusetts General HospitalThoraxklinik and National Center for Tumor Diseases (NCT) at Heidelberg University HospitalThoraxklinik and National Center for Tumor Diseases (NCT) at Heidelberg University HospitalDepartment of Anesthesiology, Heidelberg University HospitalHummingbird Diagnostics GmbHHummingbird Diagnostics GmbHHummingbird Diagnostics GmbHHummingbird Diagnostics GmbHThoraxklinik and National Center for Tumor Diseases (NCT) at Heidelberg University HospitalMRC Weatherall Institute of Molecular Medicine, University of OxfordThoraxklinik and National Center for Tumor Diseases (NCT) at Heidelberg University HospitalHummingbird Diagnostics GmbHDepartment of Anesthesiology, Heidelberg University HospitalLungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research||Department of Medicine, Christian Albrechts University of KielHummingbird Diagnostics GmbHPicower Institute for Learning and Memory, Massachusetts Institute of TechnologyHummingbird Diagnostics GmbHHummingbird Diagnostics GmbHHummingbird Diagnostics GmbH
肿瘤学医学研究方法基础医学
Jehn Julia,Schenz Judith,Muley Thomas,Pelea Oana,Kahraman Mustafa,Heuvelman Marco,N?tzel Dennis,Tikk Kaja,Daniel-Moreno Alberto,Uhle Florian,Schindler Hannah,Wu Qianxin,Reck Martin,Hofmann Sarah,Mercaldo Nathaniel,Thomas Michael,Christopoulos Petros,Uhle Sandra,Feufel Jennifer,Skottke Jasmin,Ceiler Jessika,Sikosek Tobias,Lusky Fabienne,Sauka-Spengler Tatjana,Elshiaty Mariam,Kittner Paul,Weigand Markus A,Rabe Klaus F,Rajakumar Timothy,Ferry Quentin,Steinkraus Bruno R,Hinkfoth Franziska,Horos Rastislav.A blood-based miRNA signature predicts immunotherapy efficacy in advanced stage non-small cell lung cancer[EB/OL].(2025-03-28)[2025-05-05].https://www.medrxiv.org/content/10.1101/2021.10.31.21265722.点此复制
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