title: Demethylation of cancer/testis antigens and CpG ODN stimulation enhance dendritic cell and cytotoxic T lymphocyte function in a mouse mammary model.
abstract: BACKGROUND
  Cancer/testis antigens (CTAs) are ideal targets for cancer immunotherapy in virtue of their restricted expression profile in normal tissues. However, CTA-targeted immunotherapy has been rather disappointing clinical setting for CTAs are downregulated by cytosine-phosphate-guanosine (CpG) methylation in their promoter regions, so that tumor cells have low immunogenicity.
  
  
  METHODS
  We reinduced mouse CTA P1A through demethylation process and generated P1A-specific cytotoxic lymphocytes (CTLs) by immunizing BALB/c (H-2(d)) mice with dendritic cells pulsed with a P1A-specific peptide and CpG oligodeoxynucleotide (ODN) immune adjuvant.
  
  
  RESULTS
  We found that demethylation and CpG ODN immune adjuvant stimulation facilitated DC maturation and enhanced the allogenic capacity of P1A-specific CTLs against target cells both in vitro and in vivo.
  
  
  CONCLUSIONS
  Our results suggested that CTA induction and immune adjuvant stimulation is a feasible strategy in cancer immunotherapy.
authors.affiliation: Department of Hematology, Chinese PLA General Hospital, Beijing 100853, China ; Department of Oncology, The First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Jun-Zhong
authors.initials: JZ
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Du
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Wan
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Li-li
authors.initials: LL
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010455:Peptides / Q000276:immunology; D054353:Perforin / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D054353:Perforin; D053804:Granzymes