title: Changes in immunological markers and influx of macrophages following trans-scleral thermotherapy of uveal melanoma.
abstract: OBJECTIVE
  In trans-scleral thermotherapy (TSTT), heat is applied through the sclera in order to target an intraocular uveal melanoma. Previously, it had been shown that in uveal melanoma, hyperthermia and transpupillary thermotherapy influenced expression of immunologically relevant proteins, such as S100, HLA and heat-shock proteins (HSPs). We investigated whether TSTT induced similar changes.
  
  
  METHODS
  Experimental TSTT was applied on eleven uveal melanomas prior to enucleation. Each tumour sample was processed for histopathological examination; immunohistochemical analysis was performed to determine expression of S100, HLA, HSPs and macrophage markers.
  
  
  RESULTS
  In TSTT-treated areas, expression of S100 and different HSPs was lost, while an upregulated expression of HSP GP96 was observed at the border of these areas. Expression levels of HLA-A and HLA-B varied between tumours and were not influenced by TSTT. The borders of the TSTT-treated areas showed high numbers of infiltrating macrophages, which were predominantly of the M2 phenotype.
  
  
  CONCLUSIONS
  TSTT has an effect on immunological parameters with local loss of expression of HSPs and S100. The influx of M2 macrophages around the TSTT-treated areas indicates the presence of an innate immune reaction against the induced necrosis, suggesting that TSTT-treated tumour cells are removed by a macrophage-mediated tissue repair mechanism.
authors.affiliation: Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jihan
authors.initials: J
authors.lastname: Dennaoui
authors.forename: Inge H G
authors.initials: IH
authors.lastname: Bronkhorst
authors.forename: Long V
authors.initials: LV
authors.lastname: Ly
authors.forename: Didi
authors.initials: D
authors.lastname: de Wolff-Rouendaal
authors.forename: Jan E E
authors.initials: JE
authors.lastname: Keunen
authors.forename: Nicoline E
authors.initials: NE
authors.lastname: Schalij-Delfos
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Jager
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology*; D014408:Biomarkers, Tumor / Q000276:immunology*; D002465:Cell Movement; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D006979:Hyperthermia, Induced; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D009418:S100 Proteins / Q000378:metabolism; D012590:Sclera; D014604:Uveal Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D006680:HLA Antigens; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D009418:S100 Proteins