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3-Methylcholanthrene-induced transforming growth factor-β-producing carcinomas, but not sarcomas, are refractory to regulatory T cell-depletion therapy

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Title: 3-Methylcholanthrene-induced transforming growth factor-β-producing carcinomas, but not sarcomas, are refractory to regulatory T cell-depletion therapy
Authors: Chamoto, Kenji Browse this author
Wakita, Daiko Browse this author
Ohkuri, Takayuki Browse this author
Uchinami, Yusuke Browse this author
Matsushima, Kouji Browse this author
Kitamura, Hidemitsu Browse this author
Nishimura, Takashi Browse this author
Issue Date: Apr-2010
Publisher: Wiley-Blackwell
Journal Title: Cancer Science
Volume: 101
Issue: 4
Start Page: 855
End Page: 861
Publisher DOI: 10.1111/j.1349-7006.2009.01469.x
PMID: 20151983
Abstract: Regulatory T cell (Treg) is one of the major immunosuppressors in tumor-bearing hosts. Although Treg-depletion therapy has been shown to induce a complete cure in tumor-bearing mice, this is not always successful treatment. Using 3-methylcholanthrene (MCA)-induced primary mouse tumors, we examined the distinct regulation of Treg-mediated immunosuppression between carcinomas and sarcomas. We demonstrated that the numbers of Tregs were greatly increased in SCC-bearing mice compared with sarcoma-bearing mice. This appeared to be because SCC produced higher levels of active TGF-β, which is essential for inducing Tregs, compared with sarcoma. Moreover, SCC, but not sarcomas were refractory to Treg-depletion therapy by anti-CD25 mAb administration. The refractoriness of SCC against Treg-depletion therapy was due to the rapid recovery of Tregs in SCC-bearing mice compared with sarcoma-bearing mice. However, combination treatment of anti-TGF-β mAb with anti-CD25 mAb caused a significant reduction of Treg recovery and induced a complete cure in SCC-bearing mice. Thus, we first demonstrated the refractoriness of mouse carcinoma against Treg-depletion therapy using anti-CD25 mAb administration. We also proposed a novel Treg-blocking combination therapy using anti-CD25 mAb and anti-TGF-β mAb to induce a complete cure of tumor-bearing hosts.
Rights: The definitive version is available at www.blackwell-synergy.com
Type: article (author version)
URI: http://hdl.handle.net/2115/45090
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 脇田 大功

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