Demethylation of cancer/testis antigens and CpG ODN stimulation enhance dendritic cell and cytotoxic T lymphocyte function in a mouse mammary model

Biomed Res Int. 2013;2013:196894. doi: 10.1155/2013/196894. Epub 2013 Nov 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Antigens, Neoplasm / metabolism*
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytotoxicity, Immunologic / drug effects
  • DNA Methylation / drug effects*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Granzymes / metabolism
  • Humans
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Oligodeoxyribonucleotides / pharmacology*
  • Peptides / immunology
  • Perforin / metabolism
  • Phenotype
  • Promoter Regions, Genetic / genetics
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Neoplasm
  • CPG-oligonucleotide
  • Oligodeoxyribonucleotides
  • Peptides
  • Perforin
  • Granzymes