title: Tumour-infiltrating lymphocytes and expression of programmed death ligand 1 (PD-L1) in melanoma brain metastases.
abstract: OBJECTIVE
  In this study we aimed to characterize immune infiltrates and expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) in a series of melanoma BM to provide a basis for experimental therapy using immune checkpoint inhibitors.
  
  
  RESULTS
  We investigated expression of PD-1, PD-L1, CD3, CD8, CD45RO, forkhead box protein 3 (FoxP3), CD20 and BRAF V600E by immunohistochemistry in melanoma BM samples. Forty-three specimens [27 of which (62.8%) were BRAF V600E-positive] were available. CD3(+) tumour-infiltrating lymphocytes (TILs) were evident in 33 specimens (76.7%), CD8(+) in 39 (90.7%), CD45RO(+) in 32 (74.4%), PD-1(+) in 27 (62.8%), FoxP3(+) in 21 (48.8%) and CD20(+) TILs in 19 (44.2%). Tumour PD-L1 expression was observed in 22 specimens (51.1%), and in nine of these (40.9%) expression was observed in more than 5% of tumour cells. PD-L1 expression was associated with higher density of PD-1(+) (P < 0.001), CD3(+) (P = 0.014) and FoxP3(+) (P < 0.001) TIL infiltration. Density of CD3(+) TILs was associated with density of CD8(+) (P < 0.001), PD-1(+) (P < 0.001) and CD45RO(+) (P < 0.001) TILs. PD-L1 expression or PD-1(+) , CD3(+) , CD8(+) or CD45RO(+) TILs density did not correlate with BRAF V600E status, previous systemic therapy or survival (P > 0.05).
  
  
  CONCLUSIONS
  Melanoma BM showed considerable lymphocytic infiltrates and expression of PD-L1 in the majority of investigated specimens, with high PD-L1 expression found predominantly in regions of abundant inflammation. Our data indicate that clinical studies should investigate the value of checkpoint inhibitors in patients with melanoma BMs.
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria; Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Anna Sophie
authors.initials: AS
authors.lastname: Berghoff
authors.forename: Gerda
authors.initials: G
authors.lastname: Ricken
authors.forename: Georg
authors.initials: G
authors.lastname: Widhalm
authors.forename: Orsolya
authors.initials: O
authors.lastname: Rajky
authors.forename: Karin
authors.initials: K
authors.lastname: Dieckmann
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.forename: Rupert
authors.initials: R
authors.lastname: Bartsch
authors.forename: Christoph
authors.initials: C
authors.lastname: Höller
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D008875:Middle Aged
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: brain metastases; melanoma; programmed death 1; programmed death ligand 1; tumour infiltrating lymphocytes