Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma
Background Predictive biomarkers for antibodies against programmed death 1 (PD-1) remain a major unmet need in metastatic melanoma. Specifically, response is seen in tumors that do not express programmed death ligand 1 (PD-L1), highlighting the need for a more sensitive biomarker. We hypothesize tha...
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BMJ Publishing Group
2017-12-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/5/1/25.full |
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| author | Mario Sznol Harriet M. Kluger Pok Fai Wong James W. Smithy David L. Rimm Vasiliki Pelekanou Lauren M. Moore Jamaal Rehman Patricia Gaule Veronique M. Neumeister |
| author_facet | Mario Sznol Harriet M. Kluger Pok Fai Wong James W. Smithy David L. Rimm Vasiliki Pelekanou Lauren M. Moore Jamaal Rehman Patricia Gaule Veronique M. Neumeister |
| author_sort | Mario Sznol |
| collection | DOAJ |
| description | Background Predictive biomarkers for antibodies against programmed death 1 (PD-1) remain a major unmet need in metastatic melanoma. Specifically, response is seen in tumors that do not express programmed death ligand 1 (PD-L1), highlighting the need for a more sensitive biomarker. We hypothesize that capacity to express PD-L1, as assessed by an assay for a PD-L1 transcription factor, interferon regulatory factor 1 (IRF-1), may better distinguish patients likely to benefit from anti-PD-1 immunotherapy.Methods Samples from 47 melanoma patients that received nivolumab, pembrolizumab, or combination ipilimumab/nivolumab at Yale New Haven Hospital from May 2013 to March 2016 were collected. Expression of IRF-1 and PD-L1 in archival pre-treatment formalin-fixed, paraffin-embedded tumor samples were assessed by the AQUA method of quantitative immunofluorescence. Objective radiographic response (ORR) and progression-free survival (PFS) were assessed using modified RECIST v1.1 criteria.Results Nuclear IRF-1 expression was higher in patients with partial or complete response (PR/CR) than in patients with stable or progressive disease (SD/PD) (p = 0.044). There was an insignificant trend toward higher PD-L1 expression in patients with PR/CR (p = 0.085). PFS was higher in the IRF-1-high group than the IRF-1-low group (p = 0.017), while PD-L1 expression had no effect on PFS (p = 0.83). In a subset analysis, a strong association with PFS is seen in patients treated with combination ipilimumab and nivolumab (p = 0.0051).Conclusions As a measure of PD-L1 expression capability, IRF-1 expression may be a more valuable predictive biomarker for anti-PD-1 therapy than PD-L1 itself. |
| format | Article |
| id | doaj-art-d4ac61ba98b34ae48d5cd99644bb8e16 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2017-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-d4ac61ba98b34ae48d5cd99644bb8e162025-08-20T03:10:49ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262017-12-015110.1186/s40425-017-0229-2Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanomaMario Sznol0Harriet M. Kluger1Pok Fai Wong2James W. Smithy3David L. Rimm4Vasiliki Pelekanou5Lauren M. Moore6Jamaal Rehman7Patricia Gaule8Veronique M. Neumeister94Yale University Department of Medical Oncology: Yale Cancer Center, New Haven, CT, USAAff2 0000000419368710grid.47100.32Section of Medical OncologyYale School of Medicine New Haven CT USAAff1 0000000419368710grid.47100.32Department of PathologyBML116 Yale School of Medicine PO Box 208023 310 Cedar Street 06520 New Haven CT USAAff1 0000000419368710grid.47100.32Department of PathologyBML116 Yale School of Medicine PO Box 208023 310 Cedar Street 06520 New Haven CT USAAff1 0000000419368710grid.47100.32Department of PathologyBML116 Yale School of Medicine PO Box 208023 310 Cedar Street 06520 New Haven CT USA6Bayer US, Cambridge, MA, USAAff1 0000000419368710grid.47100.32Department of PathologyBML116 Yale School of Medicine PO Box 208023 310 Cedar Street 06520 New Haven CT USAAff1 0000000419368710grid.47100.32Department of PathologyBML116 Yale School of Medicine PO Box 208023 310 Cedar Street 06520 New Haven CT USAAff1 0000000419368710grid.47100.32Department of PathologyBML116 Yale School of Medicine PO Box 208023 310 Cedar Street 06520 New Haven CT USAAff1 0000000419368710grid.47100.32Department of PathologyBML116 Yale School of Medicine PO Box 208023 310 Cedar Street 06520 New Haven CT USABackground Predictive biomarkers for antibodies against programmed death 1 (PD-1) remain a major unmet need in metastatic melanoma. Specifically, response is seen in tumors that do not express programmed death ligand 1 (PD-L1), highlighting the need for a more sensitive biomarker. We hypothesize that capacity to express PD-L1, as assessed by an assay for a PD-L1 transcription factor, interferon regulatory factor 1 (IRF-1), may better distinguish patients likely to benefit from anti-PD-1 immunotherapy.Methods Samples from 47 melanoma patients that received nivolumab, pembrolizumab, or combination ipilimumab/nivolumab at Yale New Haven Hospital from May 2013 to March 2016 were collected. Expression of IRF-1 and PD-L1 in archival pre-treatment formalin-fixed, paraffin-embedded tumor samples were assessed by the AQUA method of quantitative immunofluorescence. Objective radiographic response (ORR) and progression-free survival (PFS) were assessed using modified RECIST v1.1 criteria.Results Nuclear IRF-1 expression was higher in patients with partial or complete response (PR/CR) than in patients with stable or progressive disease (SD/PD) (p = 0.044). There was an insignificant trend toward higher PD-L1 expression in patients with PR/CR (p = 0.085). PFS was higher in the IRF-1-high group than the IRF-1-low group (p = 0.017), while PD-L1 expression had no effect on PFS (p = 0.83). In a subset analysis, a strong association with PFS is seen in patients treated with combination ipilimumab and nivolumab (p = 0.0051).Conclusions As a measure of PD-L1 expression capability, IRF-1 expression may be a more valuable predictive biomarker for anti-PD-1 therapy than PD-L1 itself.https://jitc.bmj.com/content/5/1/25.full |
| spellingShingle | Mario Sznol Harriet M. Kluger Pok Fai Wong James W. Smithy David L. Rimm Vasiliki Pelekanou Lauren M. Moore Jamaal Rehman Patricia Gaule Veronique M. Neumeister Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma Journal for ImmunoTherapy of Cancer |
| title | Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma |
| title_full | Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma |
| title_fullStr | Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma |
| title_full_unstemmed | Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma |
| title_short | Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma |
| title_sort | nuclear irf 1 expression as a mechanism to assess capability to express pd l1 and response to pd 1 therapy in metastatic melanoma |
| url | https://jitc.bmj.com/content/5/1/25.full |
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