title: Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Maria
authors.initials: M
authors.lastname: Vassilakopoulou
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece.
authors.forename: Margaritis
authors.initials: M
authors.lastname: Avgeris
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Vamsidhar
authors.initials: V
authors.lastname: Velcheti
authors.affiliation: Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kotoula
authors.affiliation: Department of Surgery (Otolaryngology), Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Theodore
authors.initials: T
authors.lastname: Rampias
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
authors.forename: Kyriakos
authors.initials: K
authors.lastname: Chatzopoulos
authors.affiliation: Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Christos
authors.initials: C
authors.lastname: Perisanidis
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece.
authors.forename: Christos K
authors.initials: CK
authors.lastname: Kontos
authors.affiliation: First Ear, Nose and Throat Clinics, Athens General Hospital "Hippokration," University of Athens, Athens, Greece.
authors.forename: Aris I
authors.initials: AI
authors.lastname: Giotakis
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: David
authors.initials: D
authors.lastname: Rimm
authors.affiliation: Department of Surgery (Otolaryngology), Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Clarence
authors.initials: C
authors.lastname: Sasaki
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
authors.affiliation: Second Department of Internal Medicine, Section of Medical Oncology, "Attikon" University Hospital, University of Athens, Athens, Greece. dpsyrri@med.uoa.gr.
authors.forename: Amanda
authors.initials: A
authors.lastname: Psyrri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000235:genetics*; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D012333:RNA, Messenger