title: Overall survival and PD-L1 expression in metastasized malignant melanoma.
abstract: BACKGROUND
  Cancers are known to elude the immune system, for example, by MHC loss, FAS up-regulation, or increased secretion of TGF-beta. Recently, ligands of coinhibitory receptors like programmed cell death ligand-1 (PD-L1, B7-H1) have come to attention for their role in tumor immune escape. Various tumors have been tested for PD-L1 expression, and conflicting results were obtained regarding its correlative impact on patient survival. This study aimed to determine the prognostic relevance of PD-L1 expression for the survival of melanoma patients.
  
  
  METHODS
  Paraffin-embedded nevi, primary melanoma, and in-transit, lymph node, and distant organ metastases from a set of 63 stages III-IV melanoma patients referred to the Netherlands Cancer Institute between 2000 and 2004 for a sentinel-node procedure or systemic therapy were studied. A large effort was invested in validating specific PD-L1 staining. In addition to immunological factors such as T-cell infiltration (CD8, CD4, and regulatory T cells), TGF-beta and MHC-I expression were assessed.
  
  
  RESULTS
  Longitudinal analysis revealed no relevant PD-L1 expression on primary melanoma compared with metastatic disease. No significant correlations with prognosis were found regarding immunological factors, whereas known prognostic markers such as Breslow thickness and sex could be confirmed. Analyses of the overall survival of our patient cohort did not reveal a negative association with PD-L1 expression.
  
  
  CONCLUSIONS
  Correlation of overall survival with PD-L1 expression by melanoma cells remains controversial, and future clinical studies should focus on antibody validation and time of analysis in respect to disease progression.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands.
authors.forename: Jules
authors.initials: J
authors.lastname: Gadiot
authors.forename: Anna I
authors.initials: AI
authors.lastname: Hooijkaas
authors.forename: Andrew D M
authors.initials: AD
authors.lastname: Kaiser
authors.forename: Harm
authors.initials: H
authors.lastname: van Tinteren
authors.forename: Hester
authors.initials: H
authors.lastname: van Boven
authors.forename: Christian
authors.initials: C
authors.lastname: Blank
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor / Q000032:analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016612:Paraffin Embedding; D011379:Prognosis; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D013194:Staining and Labeling
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human