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IFN-gamma-dependent type 1 immunity is crucial for immunosurveillance against squamous cell carcinoma in a novel mouse carcinogenesis model.
- Source :
-
Carcinogenesis [Carcinogenesis] 2009 Aug; Vol. 30 (8), pp. 1408-15. Date of Electronic Publication: 2009 Jun 09. - Publication Year :
- 2009
-
Abstract
- 3-Methylcholanthrene (MCA)-induced sarcomas have been used as conventional tools for investigating immunosurveillance against tumor development. However, MCA-induced sarcoma is not always an ideal model for the study of the human cancer system because carcinomas and not sarcomas are the dominant types of human cancers. To resolve this problem, we established a novel and simple method to induce mouse squamous cell carcinomas (SCCs). As well known, the subcutaneous injection of MCA caused the formation of sarcomas at 100% incidence. However, we here first succeeded at inducing SCC at 60% of incidence within 2 months by a single intra-dermal injection of MCA. Using this primary SCC model, we demonstrated the critical role of interferon (IFN)-gamma-dependent type 1 immunity in immunosurveillance against SCC from the following results: (i) The incidence of SCC was accelerated in IFN-gamma-deficient mice compared with that in wild-type mice; (ii) In vivo injection of CpG-oligodeoxynucleotides (CpG-ODN) caused a marked reduction in the incidence of SCC in parallel with the activation of type 1-dependent antitumor immunity and (iii) The antitumor activity of CpG-ODN was significantly decreased in IFN-gamma-deficient mice. Thus, our established MCA-induced mouse SCC model could be a powerful tool for evaluating immunosurveillance mechanisms during the development of SCC and might result in a novel strategy to address immunosurveillance mechanisms of human cancer.
- Subjects :
- Animals
Blotting, Western
Carcinogens
Carcinoma, Squamous Cell chemically induced
Carcinoma, Squamous Cell prevention & control
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Methylcholanthrene
Mice
Mice, Inbred BALB C
Mice, Knockout
Oligodeoxyribonucleotides pharmacology
RNA, Messenger genetics
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sarcoma, Experimental chemically induced
Sarcoma, Experimental prevention & control
Skin Neoplasms chemically induced
Skin Neoplasms prevention & control
Survival Rate
Carcinoma, Squamous Cell immunology
Disease Models, Animal
Immunologic Surveillance immunology
Interferon-gamma physiology
Sarcoma, Experimental immunology
Skin Neoplasms immunology
Th1 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 30
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 19509217
- Full Text :
- https://doi.org/10.1093/carcin/bgp144