title: PD-L1 expression in melanocytic lesions does not correlate with the BRAF V600E mutation.
abstract: PD-L1 expression in melanoma correlates with response to PD-1 pathway-blocking antibodies. Aberrant tumor-cell PD-L1 expression may be oncogene driven and/or induced by IFNγ. Melanomas express PD-L1 in association with tumor-infiltrating lymphocytes (TIL), but the potential contribution of the BRAF V600E mutation (BRAFmut) to induced PD-L1 expression has not been determined. Fifty-two archival melanocytic lesions were assessed for PD-L1 expression, TIL infiltration, and BRAFmut simultaneously. IFNγ-induced PD-L1 expression in cultured melanomas was assessed in parallel according to BRAF status. Melanocyte PD-L1 expression was observed in 40% of specimens, and BRAFmut was observed in 42% of specimens, but no significant concordance was found between these variables. Almost all melanocytes displaying PD-L1 expression were observed to be adjacent to TILs, irrespective of BRAF status. TIL(-) lesions were not more likely to be associated with BRAFmut, when compared with TIL(+) lesions. Baseline expression of PD-L1 by melanoma cell lines was virtually nil, regardless of BRAFmut status, and the intensity of IFN-induced PD-L1 expression in melanoma cell lines likewise did not correlate with BRAF mutational status. PD-L1 expression in melanocytic lesions does not correlate with the BRAFmut. Thus, distinct populations of melanoma patients will likely benefit from BRAF inhibitors versus PD-1 pathway blockade.
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Rodić
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors.forename: James R
authors.initials: JR
authors.lastname: Eshleman
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors.forename: Ming-Tseh
authors.initials: MT
authors.lastname: Lin
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors.forename: Haiying
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors.forename: Jung H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors.forename: Katie
authors.initials: K
authors.lastname: Beierl
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Baltimore, Maryland.
authors.forename: Shuming
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Luber
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Surgery, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Baltimore, Maryland.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Topalian
authors.affiliation: Department of Oncology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Baltimore, Maryland.
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.affiliation: Department of Pathology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland. Department of Dermatology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Baltimore, Maryland. Department of Oncology, The Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Baltimore, Maryland. jtaube1@jhmi.edu.
authors.forename: Janis M
authors.initials: JM
authors.lastname: Taube
mesh_terms: D060890:B7-H1 Antigen / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008544:Melanocytes / Q000276:immunology; D008545:Melanoma / Q000235:genetics* / Q000276:immunology / Q000556:secondary; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009506:Nevus / Q000235:genetics* / Q000276:immunology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D009363:Neoplasm Proteins; D007371:Interferon-gamma; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf