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Clin Cancer Res. 2016 Feb 1;22(3):704-13. doi: 10.1158/1078-0432.CCR-15-1543. Epub 2015 Sep 25.

Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma.

Author information

1
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
2
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece.
3
Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
4
Department of Surgery (Otolaryngology), Yale University School of Medicine, New Haven, Connecticut.
5
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
6
Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria.
7
First Ear, Nose and Throat Clinics, Athens General Hospital "Hippokration," University of Athens, Athens, Greece.
8
Second Department of Internal Medicine, Section of Medical Oncology, "Attikon" University Hospital, University of Athens, Athens, Greece. dpsyrri@med.uoa.gr.

Abstract

PURPOSE:

Programmed death-ligand 1 (PD-L1; also known as CD274 or B7-H1) expression represents a mechanism of immune escape for cancer. Our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in primary laryngeal squamous cell carcinomas (SCC).

EXPERIMENTAL DESIGN:

A well-annotated cohort of 260 operable primary laryngeal SCCs [formalin-fixed paraffin-embedded (FFPE) specimens] was morphologically characterized for stromal tumor-infiltrating lymphocytes (TIL), on hematoxylin/eosin-stained whole sections and for PD-L1 mRNA expression by qRT-PCR in FFPE specimens. For PD-L1 protein expression, automated quantitative protein analysis (AQUA) was applied on tissue microarrays consisting of two cores from these tumors. In addition, PD-L1 mRNA expression in fresh-frozen tumors and normal adjacent tissue specimens was assessed in a second independent cohort of 89 patients with primary laryngeal SCC.

RESULTS:

PD-L1 mRNA levels were upregulated in tumors compared with surrounding normal tissue (P = 0.009). TILs density correlated with tumor PD-L1 AQUA levels (P = 0.021). Both high TILs density and high PD-L1 AQUA levels were significantly associated with superior disease-free survival (DFS; TILs: P = 0.009 and PD-L1: P = 0.044) and overall survival (OS; TILs: P = 0.015 and PD-L1: P = 0.059) of the patients and retained significance in multivariate analysis.

CONCLUSIONS:

Increased TILs density and PD-L1 levels are associated with better outcome in laryngeal squamous cell cancer. Assessment of TILs and PD-L1 expression could be useful to predict response to immune checkpoint inhibitors.

PMID:
26408403
DOI:
10.1158/1078-0432.CCR-15-1543
[Indexed for MEDLINE]
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