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Carcinogenesis Advance Access published online on June 9, 2009
Carcinogenesis, doi:10.1093/carcin/bgp144
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Published by Oxford University Press 2009.

IFN-{gamma}-dependent type 1 immunity is crucial for immunosurveillance against squamous cell carcinoma in a novel mouse carcinogenesis model

Daiko Wakita1, Kenji Chamoto1, Takayuki Ohkuri1, Yoshinori Narita1, Shigeru Ashino1, Kentaro Sumida1, Hiroyoshi Nishikawa2, Hiroshi Shiku2, Yuji Togashi3, Hidemitsu Kitamura1 and Takashi Nishimura1,3

1 Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo 001-0021, Japan
2 Department of Cancer Vaccine, Mie University Graduate School of Medicine, Mie, 514-8507, Japan
3 Division of ROYCE' Health Bioscience, Institute for Genetic Medicine, Hokkaido University, Sapporo, 001-0021, Japan

Address correspondence and reprint requests to Dr. Takashi Nishimura, Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-21, Nishi-11, Kita-ku, Sapporo 001-0021, Japan Phone and Fax number: +81-11-706-7546, E-mail address: tak24{at}igm.hokudai.ac.jp

Three-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 (SCC). 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 intradermal injection of MCA. Using this primary SCC model, we demonstrated the critical role of 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-ODN caused a marked reduction in the incidence of SCC in parallel with the activation of type 1-dependent antitumor immunity; (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.

Key Words: IFN-gamma • carcinogenesis • immunosurveillance • squamous cell carcinoma • CpG-ODN

This work was supported in part by a Grant-in-Aid for Ministry of Education, Culture, Sports, Science and Technology (H.K. and T.N.), by a National Project "Knowledge Cluster Initiative" (2nd stage, "Sapporo Biocluster Bio-S"), Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT), and by a JSPS Research Fellowships for Young Scientists (D.W. and T.O).

Received January 10, 2009; revised June 2, 2009; accepted June 2, 2009.


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