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Carcinogenesis Advance Access originally published online on June 9, 2009
Carcinogenesis 2009 30(8):1408-1415; 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, Kita-21, Nishi-11, Kita-ku, 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

* To whom correspondence should be addressed. Tel: +81 11 706 7546; Fax: +81 11 706 7546; Email: tak24{at}igm.hokudai.ac.jp

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.

Abbreviations: CpG-ODN, CpG-oligodeoxynucleotides; DLN, draining lymph node; i.d., intra-dermal; IFN, interferon; IL, interleukin; mAb, monoclonal antibody; MCA, 3-methylcholanthrene; s.c., subcutaneous; SCC, squamous cell carcinoma; WT, wild-type

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


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