Development and validation of blood-based predictive biomarkers for response to PD-(L)-1 checkpoint inhibitors: evidence of a universal systemic core of 3D immunogenetic profiling across multiple oncological indications
Development and validation of blood-based predictive biomarkers for response to PD-(L)-1 checkpoint inhibitors: evidence of a universal systemic core of 3D immunogenetic profiling across multiple oncological indications
Abstract Unprecedented advantages in cancer treatment with immune checkpoint inhibitors (ICI) remain limited to a subset of patients. Systemic analyses of the regulatory 3D genome architecture linked to individual epigenetics and immunogenetic controls associated with tumour immune evasion mechanisms and immune checkpoint pathways reveals a highly prevalent patient molecular profiles predictive of response to PD-(L)1 immune checkpoint inhibitors. A clinical blood test based on the set of 8 3D genomic biomarkers has been developed and validated on several independent cancer patient cohorts to predict response to PD-(L)1 immune checkpoint inhibition. The predictive 8 biomarker set is derived from prospective observational clinical trials, representing 229 treatments with Pembrolizumab, Atezolizumab, Durvalumab, in diverse indications: melanoma, non-small cell lung, urethral, hepatocellular, bladder, prostate cancer, head and neck, vulvar, colon, breast, bone, brain, lymphoma, larynx cancer, and cervix cancers. The 3D genomic 8 biomarker panel for response to immune checkpoint therapy achieved high accuracy up to 85%, sensitivity of 93% and specificity of 82%. This study demonstrates that a 3D genomic approach could be used to develop a predictive clinical assay for response to PD-(L)1 checkpoint inhibition in cancer patients.
Wilson Adam、Salter Matthew、Westra Jurjen W.、Egan Benedict、Green Jayne、Keat Cheah Soon、Suan Ang Tick、Fatt Ho Kean、Wei Luen Fabian Lee、Guiel Thomas、Heaton Robert Jr、Akoulitchev Alexandre、Santos Francisco C.、Thacker Morgan、Lim Chun Ren、Dezfouli Mehrnoush、Koutsothanasi Christina、Levine Jedd、Hunter Ewan、Parnall Matthew、Dring Ann、Ng Serene、Raman Rakesh、Ramadass Aroul、Powell Ryan
Oxford BioDynamics PlcOxford BioDynamics PlcOxford BioDynamics PlcOxford BioDynamics PlcOxford BioDynamics PlcMount Miriam Cancer Hospital (MMCH)||Island HospitalMount Miriam Cancer Hospital (MMCH)Mount Miriam Cancer Hospital (MMCH)Mount Miriam Cancer Hospital (MMCH)Oxford BioDynamics Inc.Oxford BioDynamics Inc.Oxford BioDynamics PlcOxford BioDynamics PlcOxford BioDynamics PlcOxford BioDynamics (M) Sdn BhdOxford BioDynamics PlcOxford BioDynamics PlcOxford BioDynamics Inc.Oxford BioDynamics PlcOxford BioDynamics PlcOxford BioDynamics PlcOxford BioDynamics (M) Sdn BhdMount Miriam Cancer Hospital (MMCH)Oxford BioDynamics PlcOxford BioDynamics Plc
医学研究方法肿瘤学生物科学研究方法、生物科学研究技术
Wilson Adam,Salter Matthew,Westra Jurjen W.,Egan Benedict,Green Jayne,Keat Cheah Soon,Suan Ang Tick,Fatt Ho Kean,Wei Luen Fabian Lee,Guiel Thomas,Heaton Robert Jr,Akoulitchev Alexandre,Santos Francisco C.,Thacker Morgan,Lim Chun Ren,Dezfouli Mehrnoush,Koutsothanasi Christina,Levine Jedd,Hunter Ewan,Parnall Matthew,Dring Ann,Ng Serene,Raman Rakesh,Ramadass Aroul,Powell Ryan.Development and validation of blood-based predictive biomarkers for response to PD-(L)-1 checkpoint inhibitors: evidence of a universal systemic core of 3D immunogenetic profiling across multiple oncological indications[EB/OL].(2025-03-28)[2025-05-25].https://www.medrxiv.org/content/10.1101/2021.12.21.21268094.点此复制
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