Nuclear IRF-1 expression as a mechanism to assess “Capability” to express PD-L1 and response to PD-1 therapy in metastatic melanoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

James W. Smithy, Lauren M. Moore, Vasiliki Pelekanou, Jamaal Rehman, Patricia Gaule, Pok Fai Wong, Veronique M. Neumeister, Mario Sznol, Harriet M. Kluger, David L. Rimm

ABSTRACT

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. More... »

PAGES

25

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40425-017-0229-2

DOI

http://dx.doi.org/10.1186/s40425-017-0229-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084252941

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28331615


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    "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.\nMETHODS: 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.\nRESULTS: 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\u2009=\u20090.044). There was an insignificant trend toward higher PD-L1 expression in patients with PR/CR (p\u2009=\u20090.085). PFS was higher in the IRF-1-high group than the IRF-1-low group (p\u2009=\u20090.017), while PD-L1 expression had no effect on PFS (p\u2009=\u20090.83). In a subset analysis, a strong association with PFS is seen in patients treated with combination ipilimumab and nivolumab (p\u2009=\u20090.0051).\nCONCLUSIONS: 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.", 
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