title: Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites.
abstract: OBJECTIVE
  Programmed death ligand-1 (PD-L1) tumor expression represents a mechanism of immune escape for melanoma cells. Drugs blocking PD-L1 or its receptor have shown unprecedented activity in melanoma, and our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in metastatic melanomas.
  
  
  METHODS
  We used a tissue microarray (TMA) consisting of two cores from 95 metastatic melanomas characterized for clinical stage, outcome, and anatomic site of disease. We assessed PD-L1 expression and tumor-infiltrating lymphocyte (TIL) content (total T cells and CD4/CD8 subsets) by quantitative immunofluorescence.
  
  
  RESULTS
  High PD-L1 expression was associated with improved survival (P = 0.02) and higher T-cell content (P = 0.0005). Higher T-cell content (total and CD8 cells) was independently associated with improved overall survival; PD-L1 expression was not independently prognostic. High TIL content in extracerebral metastases was associated with increased time to developing brain metastases (P = 0.03). Cerebral and dermal metastases had slightly lower PD-L1 expression than other sites, not statistically significant. Cerebral metastases had less T cells (P = 0.01).
  
  
  CONCLUSIONS
  T-cell-infiltrated melanomas, particularly those with high CD8 T-cell content, are more likely to be associated with PD-L1 expression in tumor cells, an improved prognosis, and increased time to development of brain metastases. Studies of T-cell content and subsets should be incorporated into trials of PD-1/PD-L1 inhibitors to determine their predictive value. Furthermore, additional studies of anatomic sites with less PD-L1 expression and T-cell infiltrate are needed to determine if discordant responses to PD-1/PD-L1 inhibitors are seen at those sites.
authors: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut. harriet.kluger@yale.edu.
authors: Harriet M
authors: HM
authors: Kluger
authors: Department of Biology, School of Health and Natural Sciences, University of Saint Joseph, West Hartford, Connecticut.
authors: Christopher R
authors: CR
authors: Zito
authors: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors: Meaghan L
authors: ML
authors: Barr
authors: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors: Marina K
authors: MK
authors: Baine
authors: Department of Neurosurgery and Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut.
authors: Veronica L S
authors: VL
authors: Chiang
authors: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors: Mario
authors: M
authors: Sznol
authors: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
authors: David L
authors: DL
authors: Rimm
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut.
authors: Lieping
authors: L
authors: Chen
authors: Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors: Lucia B
authors: LB
authors: Jilaveanu
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D008875:Middle Aged; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human