title: Expression of synovial sarcoma X (SSX) antigens in epithelial ovarian cancer and identification of SSX-4 epitopes recognized by CD4+ T cells.
abstract: OBJECTIVE
  Synovial sarcoma X (SSX) breakpoint genes are expressed in a variety of cancers but not in normal tissues, except for testis, and are potential targets for immunotherapy. The aims of this study were to determine the expression and immunogenicity of these antigens in patients with epithelial ovarian cancer (EOC).
  
  
  METHODS
  SSX-1-, SSX-2-, and SSX-4-specific reverse transcription-PCR were done on a panel of EOC specimens. Sera from a subgroup of the patients were tested for SSX-2 and SSX-4 antibody by ELISA and recombinant antigen expression on yeast surface (RAYS). In vitro stimulation of peripheral blood mononuclear cells from a patient bearing SSX-4-expressing tumor with a pool of long peptides spanning the protein sequence was used for assessment of SSX-4-specific CD4(+) T cells recognizing distinct antigenic sequences restricted by HLA class II alleles.
  
  
  RESULTS
  Our results indicate expression of SSX-1, SSX-2, and SSX-4 in 2.5%, 10%, and 16% of 120 EOC specimens, respectively. When all three SSX antigens are considered, aberrant expression was found in 26% of ovarian tumors. Antibodies to SSX-2 and SSX-4 were detectable by ELISA and RAYS in two patients. SSX-4-specific CD4(+) T cells recognizing two previously undescribed SSX-4-derived T-cell epitopes in association with HLA-DR (SSX-4: 51-70 and SSX-4: 61-180) were identified.
  
  
  CONCLUSIONS
  Our study shows aberrant expression of SSX antigens in a proportion of patients with EOC. The evidence of humoral immunity to SSX-2 and SSX-4, and SSX-4-specific CD4(+) T cells among circulating lymphocytes in patients with antigen expressing EOC suggest that these antigens are attractive targets for specific immunotherapy in EOC.
authors.affiliation: Ludwig Institute Clinical Trial Center, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.forename: Christoph
authors.initials: C
authors.lastname: Renner
authors.forename: Andrea
authors.initials: A
authors.lastname: Merlo
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Sacha
authors.initials: S
authors.lastname: Gjnatic
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Stockert
authors.forename: Deborah
authors.initials: D
authors.lastname: Driscoll
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000097:blood; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000401:mortality; D011379:Prognosis; D012097:Repressor Proteins / Q000276:immunology*; D015996:Survival Rate
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins