title: A potential role for immunotherapy in thyroid cancer by enhancing NY-ESO-1 cancer antigen expression.
abstract: BACKGROUND
  NY-ESO-1 is one of the most immunogenic members of the cancer/testis antigen family and its levels can be increased after exposure to demethylating and deacetylating agents. This cytoplasmic antigen can serve as a potent target for cancer immunotherapy and yet has not been well studied in differentiated thyroid cancer cells.
  
  
  METHODS
  We studied the baseline expression of NY-ESO-1 messenger RNA and protein before and after exposure to 5-aza-2'-deoxycytidine (DAC) (72 hours) in a panel of thyroid cancer cell lines using quantitative polymerase chain reaction and Western blot. HLA-A2+, NY-ESO-1+ thyroid cell lines were then co-cultured with peripheral blood lymphocytes transduced with NY-ESO-1 specific T-cell receptor (TCR) and assayed for interferon-gamma and Granzyme-B release in the medium. SCID mice injected orthotopically with BCPAP cells were treated with DAC to evaluate for NY-ESO-1 gene expression in vivo.
  
  
  RESULTS
  None of the thyroid cancer cell lines showed baseline expression of NY-ESO-1. Three cell lines, BCPAP, TPC-1, and 8505c, showed an increase in NY-ESO-1 gene expression with DAC treatment and were found to be HLA-A2 positive. DAC-treated target BCPAP and TPC-1 tumor cells with up-regulated NY-ESO-1 levels were able to mount an appropriate interferon-gamma and Granzyme-B response upon co-culture with the NY-ESO-1-TCR-transduced peripheral blood lymphocytes. In vivo DAC treatment was able to increase NY-ESO-1 expression in an orthotopic mouse model with BCPAP cells.
  
  
  CONCLUSIONS
  Our data suggest that many differentiated thyroid cancer cells can be pressed to express immune antigens, which can then be utilized in TCR-based immunotherapeutic interventions.
authors.affiliation: 1 Massachusetts General Hospital , Harvard Medical School, Boston, Massachusetts.
authors.forename: Viswanath
authors.initials: V
authors.lastname: Gunda
authors.forename: Dennie T
authors.initials: DT
authors.lastname: Frederick
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Bernasconi
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Wargo
authors.forename: Sareh
authors.initials: S
authors.lastname: Parangi
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003593:Cytoplasm / Q000378:metabolism; D000077209:Decitabine; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D000077209:Decitabine; D007371:Interferon-gamma; D053804:Granzymes; D001374:Azacitidine