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

2017-03-21

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

BackgroundPredictive 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.MethodsSamples 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.ResultsNuclear 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).ConclusionsAs 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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34 schema:description BackgroundPredictive 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.MethodsSamples 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.ResultsNuclear 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).ConclusionsAs 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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40 schema:keywords AQUA method
41 Cr
42 IRF-1
43 IRF-1 expression
44 MethodsSamples
45 New Haven Hospital
46 PD-1 therapy
47 PD-L1
48 PD-L1 expression
49 PR/CR
50 RECIST v1.1 criteria
51 Yale-New Haven Hospital
52 analysis
53 anti-PD-1 immunotherapy
54 anti-PD-1 therapy
55 antibodies
56 assays
57 association
58 biomarkers
59 capability
60 capacity
61 combination ipilimumab
62 combination ipilimumab/nivolumab
63 complete response
64 criteria
65 death ligand 1
66 death-1
67 disease
68 effect
69 expression
70 expression capability
71 factor 1
72 factors
73 formalin
74 group
75 high PD-L1 expression
76 hospital
77 immunofluorescence
78 immunotherapy
79 insignificant trend
80 interferon regulatory factor 1
81 ipilimumab
82 ipilimumab/nivolumab
83 ligand 1
84 major unmet need
85 measures
86 mechanism
87 melanoma
88 melanoma patients
89 metastatic melanoma
90 method
91 need
92 nivolumab
93 objective radiographic response
94 paraffin
95 patients
96 pre-treatment formalin
97 predictive biomarkers
98 progression-free survival
99 progressive disease
100 quantitative immunofluorescence
101 radiographic response
102 regulatory factor 1
103 response
104 samples
105 sensitive biomarker
106 strong association
107 subset analysis
108 survival
109 therapy
110 transcription factors
111 trends
112 tumor samples
113 tumors
114 unmet need
115 valuable predictive biomarker
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