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J Immunother Cancer. 2017 Mar 21;5:25. doi: 10.1186/s40425-017-0229-2. eCollection 2017.

Nuclear IRF-1 expression as a mechanism to assess "Capability" to express PD-L1 and response to PD-1 therapy in metastatic melanoma.

Author information

1
Department of Pathology, BML116 Yale School of Medicine, 310 Cedar Street, PO Box 208023, 06520 New Haven, CT USA.
2
Section of Medical Oncology, Yale School of Medicine, New Haven, CT USA.

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.

KEYWORDS:

Biomarkers; IRF-1; Melanoma; PD-L1

PMID:
28331615
PMCID:
PMC5359951
DOI:
10.1186/s40425-017-0229-2
[Indexed for MEDLINE]
Free PMC Article

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