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