Most cited article - PubMed ID 12579325
Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: Effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines
BACKGROUND: Epigenetic mechanisms have important roles in the tumour escape from immune responses, such as in MHC class I downregulation or altered expression of other components involved in antigen presentation. Chemotherapy with DNA methyltransferase inhibitors (DNMTi) can thus influence the tumour cell interactions with the immune system and their sensitivity to immunotherapy. METHODS: We evaluated the therapeutic effects of the DNMTi 5-azacytidine (5AC) against experimental MHC class I-deficient and -positive tumours. The 5AC therapy was combined with immunotherapy, using a murine model for HPV16-associated tumours. RESULTS: We have demonstrated 5AC additive effects against MHC class I-positive and -deficient tumours when combined with unmethylated CpG oligodeoxynucleotides or with IL-12-producing cellular vaccine. The efficacy of the combined chemoimmunotherapy against originally MHC class I-deficient tumours was partially dependent on the CD8(+)-mediated immune responses. Increased cell surface expression of MHC class I cell molecules, associated with upregulation of the antigen-presenting machinery-related genes, as well as of genes encoding selected components of the IFNγ-signalling pathway in tumours explanted from 5AC-treated animals, were observed. CONCLUSION: Our data suggest that chemotherapy of MHC class I-deficient tumours with 5AC combined with immunotherapy is an attractive setting in the treatment of MHC class I-deficient tumours.
- MeSH
- Azacitidine pharmacology MeSH
- DNA Primers MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Neoplasms, Experimental drug therapy immunology therapy virology MeSH
- Immunotherapy * MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Human papillomavirus 16 isolation & purification MeSH
- Methylation MeSH
- Histocompatibility Antigens Class I immunology MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Antimetabolites, Antineoplastic pharmacology MeSH
- Base Sequence MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Azacitidine MeSH
- DNA Primers MeSH
- Histocompatibility Antigens Class I MeSH
- Antimetabolites, Antineoplastic MeSH
