PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine
Background Anti-programmed cell death protein 1 and programmed cell death ligand 1 (PD-L1) agents are broadly used in first-line and second-line treatment across different tumor types. While immunohistochemistry-based assays are routinely used to assess PD-L1 expression, their clinical utility remai...
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BMJ Publishing Group
2021-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/10/e002179.full |
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| author | Mariaelena Pierobon Johann De Bono Ruth Riisnaes Giuseppe Giaccone Matthew Blackburn Lance Liotta Vienna Ludovini Neil J Shah Giuseppina Improta Antonella Ravaggi Niven Mehra Angelo Sidoni Elisa Baldelli K Alex Hodge Guido Bellezza Guido Gambara Martina Mandarano Chamodya Ruhunusiri Bryant Dunetz Maysa Abu-Khalaf Julia Wulfkuhle Rosa I Gallagher Franco Odicino Maria Isabella Sereni Angela Zupa Perry Demsko Lucio Crino' Emanuel F Petricoin |
| author_facet | Mariaelena Pierobon Johann De Bono Ruth Riisnaes Giuseppe Giaccone Matthew Blackburn Lance Liotta Vienna Ludovini Neil J Shah Giuseppina Improta Antonella Ravaggi Niven Mehra Angelo Sidoni Elisa Baldelli K Alex Hodge Guido Bellezza Guido Gambara Martina Mandarano Chamodya Ruhunusiri Bryant Dunetz Maysa Abu-Khalaf Julia Wulfkuhle Rosa I Gallagher Franco Odicino Maria Isabella Sereni Angela Zupa Perry Demsko Lucio Crino' Emanuel F Petricoin |
| author_sort | Mariaelena Pierobon |
| collection | DOAJ |
| description | Background Anti-programmed cell death protein 1 and programmed cell death ligand 1 (PD-L1) agents are broadly used in first-line and second-line treatment across different tumor types. While immunohistochemistry-based assays are routinely used to assess PD-L1 expression, their clinical utility remains controversial due to the partial predictive value and lack of standardized cut-offs across antibody clones. Using a high throughput immunoassay, the reverse phase protein microarray (RPPA), coupled with a fluorescence-based detection system, this study compared the performance of six anti-PD-L1 antibody clones on 666 tumor samples.Methods PD-L1 expression was measured using five antibody clones (22C3, 28–8, CAL10, E1L3N and SP142) and the therapeutic antibody atezolizumab on 222 lung, 71 ovarian, 52 prostate and 267 breast cancers, and 54 metastatic lesions. To capture clinically relevant variables, our cohort included frozen and formalin-fixed paraffin-embedded samples, surgical specimens and core needle biopsies. Pure tumor epithelia were isolated using laser capture microdissection from 602 samples. Correlation coefficients were calculated to assess concordance between antibody clones. For two independent cohorts of patients with lung cancer treated with nivolumab, RPPA-based PD-L1 measurements were examined along with response to treatment.Results Median-center PD-L1 dynamic ranged from 0.01 to 39.37 across antibody clones. Correlation coefficients between the six antibody clones were heterogeneous (range: −0.48 to 0.95) and below 0.50 in 61% of the comparisons. In nivolumab-treated patients, RPPA-based measurement identified a subgroup of tumors, where low PD-L1 expression equated to lack of response.Conclusions Continuous RPPA-based measurements capture a broad dynamic range of PD-L1 expression in human specimens and heterogeneous concordance levels between antibody clones. This high throughput immunoassay can potentially identify subgroups of tumors in which low expression of PD-L1 equates to lack of response to treatment. |
| format | Article |
| id | doaj-art-b20bc5349766429ca47d7ba6932e2280 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-b20bc5349766429ca47d7ba6932e22802025-08-20T03:04:47ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-10-0191010.1136/jitc-2020-002179PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicineMariaelena Pierobon0Johann De Bono1Ruth Riisnaes2Giuseppe Giaccone3Matthew Blackburn4Lance Liotta5Vienna Ludovini6Neil J Shah7Giuseppina Improta8Antonella Ravaggi9Niven Mehra10Angelo Sidoni11Elisa Baldelli12K Alex Hodge13Guido Bellezza14Guido Gambara15Martina Mandarano16Chamodya Ruhunusiri17Bryant Dunetz18Maysa Abu-Khalaf19Julia Wulfkuhle20Rosa I Gallagher21Franco Odicino22Maria Isabella Sereni23Angela Zupa24Perry Demsko25Lucio Crino'26Emanuel F Petricoin27School of Systems Biology, George Mason University, Manassas, Virginia, USAregius professor of cancer research and professor in experimental cancer medicineThe Institute of Cancer Research, London, UKDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USADepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USADivision of Medical Oncology, S. Maria della Misericordia Hospital, Perugia, ItalyDepartment of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USAAngelo Nocivelli Institute of Molecular Medicine, Division of Gynecologic Oncology, University of Brescia and ASST Spedali Civili di Brescia, Brescia, ItalyThe Institute of Cancer Research, London, UKDepartment of Experimental Medicine, Section of Anatomic Pathology and Histology, University of Perugia, Perugia, ItalyCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USADepartment of Experimental Medicine, Section of Anatomic Pathology and Histology, University of Perugia, Perugia, ItalyCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USADepartment of Experimental Medicine, Section of Anatomic Pathology and Histology, University of Perugia, Perugia, ItalyCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USASide Out Foundation, Fairfax, Virginia, USADepartment of Medical Oncology, Sidney Kimmel Cancer Center at Jefferson Health, Thomas Jefferson University, Philadelphia, Pennsylvania, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USADepartment of Clinical and Experimental Sciences, University of Brescia, Brescia, ItalyCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USACenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USADepartment of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, ItalyCenter for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia, USABackground Anti-programmed cell death protein 1 and programmed cell death ligand 1 (PD-L1) agents are broadly used in first-line and second-line treatment across different tumor types. While immunohistochemistry-based assays are routinely used to assess PD-L1 expression, their clinical utility remains controversial due to the partial predictive value and lack of standardized cut-offs across antibody clones. Using a high throughput immunoassay, the reverse phase protein microarray (RPPA), coupled with a fluorescence-based detection system, this study compared the performance of six anti-PD-L1 antibody clones on 666 tumor samples.Methods PD-L1 expression was measured using five antibody clones (22C3, 28–8, CAL10, E1L3N and SP142) and the therapeutic antibody atezolizumab on 222 lung, 71 ovarian, 52 prostate and 267 breast cancers, and 54 metastatic lesions. To capture clinically relevant variables, our cohort included frozen and formalin-fixed paraffin-embedded samples, surgical specimens and core needle biopsies. Pure tumor epithelia were isolated using laser capture microdissection from 602 samples. Correlation coefficients were calculated to assess concordance between antibody clones. For two independent cohorts of patients with lung cancer treated with nivolumab, RPPA-based PD-L1 measurements were examined along with response to treatment.Results Median-center PD-L1 dynamic ranged from 0.01 to 39.37 across antibody clones. Correlation coefficients between the six antibody clones were heterogeneous (range: −0.48 to 0.95) and below 0.50 in 61% of the comparisons. In nivolumab-treated patients, RPPA-based measurement identified a subgroup of tumors, where low PD-L1 expression equated to lack of response.Conclusions Continuous RPPA-based measurements capture a broad dynamic range of PD-L1 expression in human specimens and heterogeneous concordance levels between antibody clones. This high throughput immunoassay can potentially identify subgroups of tumors in which low expression of PD-L1 equates to lack of response to treatment.https://jitc.bmj.com/content/9/10/e002179.full |
| spellingShingle | Mariaelena Pierobon Johann De Bono Ruth Riisnaes Giuseppe Giaccone Matthew Blackburn Lance Liotta Vienna Ludovini Neil J Shah Giuseppina Improta Antonella Ravaggi Niven Mehra Angelo Sidoni Elisa Baldelli K Alex Hodge Guido Bellezza Guido Gambara Martina Mandarano Chamodya Ruhunusiri Bryant Dunetz Maysa Abu-Khalaf Julia Wulfkuhle Rosa I Gallagher Franco Odicino Maria Isabella Sereni Angela Zupa Perry Demsko Lucio Crino' Emanuel F Petricoin PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine Journal for ImmunoTherapy of Cancer |
| title | PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine |
| title_full | PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine |
| title_fullStr | PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine |
| title_full_unstemmed | PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine |
| title_short | PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine |
| title_sort | pd l1 quantification across tumor types using the reverse phase protein microarray implications for precision medicine |
| url | https://jitc.bmj.com/content/9/10/e002179.full |
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