Development and validation of blood-based predictive biomarkers for response to PD-1/PD-L1 checkpoint inhibitors: Evidence of a universal systemic core of 3D immunogenetic profiling across multiple oncological indications

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Hunter, Ewan, Salter, Matthew, Powell, Ryan, Dring, Ann, Naithani, Tarun, Chatziioannou, Maria Eleni, Gebregzabhar, Abel, Issa, Mutaz, Green, Jayne, Ng, Serene, Lim, Chun Ren, Keat, Cheah Soon, Suan, Ang Tick, Raman, Rakesh, Fatt, Ho Kean, Luen, Fabian Lee Wei, Alshaker, Heba, Pchejetski, Dmitri, Blum, Dave, Guiel, Thomas, Heaton, Robert, Levine, Jedd and Akoulitchev, Alexandre (2023) Development and validation of blood-based predictive biomarkers for response to PD-1/PD-L1 checkpoint inhibitors: Evidence of a universal systemic core of 3D immunogenetic profiling across multiple oncological indications. Cancers, 15 (10). ISSN 2072-6694

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Abstract

Background: Unprecedented advantages in cancer treatment with immune checkpoint inhibitors (ICIs) remain limited to only a subset of patients. Systemic analyses of the regulatory 3D genome architecture linked to individual epigenetic and immunogenetic controls associated with tumour immune evasion mechanisms and immune checkpoint pathways reveal a highly prevalent molecular profile predictive of response to PD-1/PD-L1 ICIs. A clinical blood test based on a set of eight (8) 3D genomic biomarkers has been developed and validated on the basis of an observational trial to predict response to ICI therapy. Methods: The predictive eight biomarker set is derived from prospective observational clinical trials, representing 280 treatments with Pembrolizumab, Atezolizumab, Durvalumab, Nivolumab, and Avelumab in a broad range of indications: melanoma, lung, hepatocellular, renal, breast, bladder, colon, head and neck, bone, brain, lymphoma, prostate, vulvar, and cervical cancers. Results: The 3D genomic eight biomarker panel for response to immune checkpoint therapy achieved a high accuracy of 85%, sensitivity of 93%, and specificity of 82%. Conclusions: This study demonstrates that a 3D genomic approach can be used to develop a predictive clinical assay for response to PD-1/PD-L1 checkpoint inhibition in cancer patients.

Item Type:	Article
Additional Information:	Data Availability Statement: The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Funding: This work is part of the program funded by Oxford BioDynamics Plc and by the award “Development and validation of baseline blood-based epigenetic biomarkers for predicting non-responders to ICB monotherapies” by PACT, FNIH, USA (2021-PACT001).
Uncontrolled Keywords:	blood test,epigenetics,immune checkpoint inhibitors,immuno-oncology,response to treatment,oncology,cancer research,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2730
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	21 Jul 2025 10:35
Last Modified:	21 Jul 2025 11:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99960
DOI:	10.3390/cancers15102696

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