title: Expression, epigenetic regulation, and humoral immunogenicity of cancer-testis antigens in chronic myeloid leukemia.
abstract: OBJECTIVE
  Cancer-testis (CT) antigens represent attractive targets for tumor immunotherapy based on their tumor-restricted expression and immunogenicity. However, a broad picture of the expression of CT antigens and associated humoral immune responses in chronic myeloid leukemia (CML) is still missing.
  
  
  METHODS
  We screened CML cell lines and bone marrow (BM) samples from healthy donors by RT-PCR for the expression of 31 CT antigens before and after treatment with epigenetic agents. Expression of tumor-restricted antigens was further examined in 60 CML patients and humoral immune responses against 15 CT antigens were screened by ELISA.
  
  
  RESULTS
  In untreated cell lines we detected the expression of 17 CT antigens that were absent from normal BM. Expression of most antigens increased following demethylating treatment with 5'-Aza-2'-Deoxycytidine. In these samples, only PRAME was repeatedly detected and expression correlated with several clinicopathological parameters and decreased overall survival. We further show that a lower frequency of PRAME-positive samples during imatinib treatment was not caused by gene-specific downregulation. Analyzing the patients' antibody responses we found that the vast majority of patients lacked spontaneous immunity against CT antigens including PRAME.
  
  
  CONCLUSIONS
  CT antigen expression can be increased by the application of epigenetic agents and the expression of PRAME correlates with clinicopathological parameters and overall survival in patients with CML, but does not lead to humoral immune responses. PRAME-specific immunotherapy might represent a promising approach for the eradication of residual therapy-resistant leukemic cells due to its frequent expression and stability under imatinib treatment.
authors.affiliation: Department of Oncology and Hematology, Center of Oncology, Hamburg, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Luetkens
authors.forename: Phillipe
authors.initials: P
authors.lastname: Schafhausen
authors.forename: Frederike
authors.initials: F
authors.lastname: Uhlich
authors.forename: Tim
authors.initials: T
authors.lastname: Stasche
authors.forename: Ruken
authors.initials: R
authors.lastname: Akbulak
authors.forename: Britta M
authors.initials: BM
authors.lastname: Bartels
authors.forename: York
authors.initials: Y
authors.lastname: Hildebrandt
authors.forename: Arthur
authors.initials: A
authors.lastname: Gontarewicz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kobold
authors.forename: Sabrina
authors.initials: S
authors.lastname: Meyer
authors.forename: Maja
authors.initials: M
authors.lastname: Gordic
authors.forename: Katrin
authors.initials: K
authors.lastname: Bartels
authors.forename: Nesrine
authors.initials: N
authors.lastname: Lajmi
authors.forename: Yanran
authors.initials: Y
authors.lastname: Cao
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Djordje
authors.initials: D
authors.lastname: Atanackovic
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001549:Benzamides; D000077209:Decitabine; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000276:immunology; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D000068877:Imatinib Mesylate; D056724:Immunity, Humoral / Q000187:drug effects / Q000276:immunology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000276:immunology / Q000378:metabolism; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000077209:Decitabine; D000068877:Imatinib Mesylate; D001374:Azacitidine