IFN-gamma-dependent type 1 immunity is crucial for immunosurveillance against squamous cell carcinoma in a novel mouse carcinogenesis model.
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.
Wakita
Daiko
D
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-21, Nishi-11, Kita-ku, Sapporo 001-0021, Japan.
Chamoto
Kenji
K
Ohkuri
Takayuki
T
Narita
Yoshinori
Y
Ashino
Shigeru
S
Sumida
Kentaro
K
Nishikawa
Hiroyoshi
H
Shiku
Hiroshi
H
Togashi
Yuji
Y
Kitamura
Hidemitsu
H
Nishimura
Takashi
T
D000818:Animals; D015153:Blotting, Western; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007157:Immunologic Surveillance / Q000276:immunology*; D007371:Interferon-gamma / Q000502:physiology*; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D012878:Skin Neoplasms / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D015996:Survival Rate; D018417:Th1 Cells / Q000276:immunology*
C408982:CPG-oligonucleotide; D002273:Carcinogens; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D008748:Methylcholanthrene; D007371:Interferon-gamma