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- W2037701082 abstract "Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCIt has been demonstrated that lymphodepletion by cytotoxic regimens, such as chemotherapy and radiotherapy, augments antitumor immune response. Although the mechanism underlying this stimulation of antitumor immunity remains unclear, possible explanations have been proposed; depletion of suppressor cells, improvement of tumor-antigen presentation, and elimination of lymphocytes competing activation cytokines. We previously reported that CD4+CD25+Foxp3+ regulatory T cells were increasing in sublethally (500 rad) irradiated mice. Those radio-resistant regulatory T cells inhibited the development of antitumor immunity during recovery from lymphopenia. Depletion of regulatory T cells after irradiation enhanced generation of antitumor effector T cells and significantly suppressed tumor progression.We hypothesized that chemotherapy-resistant, as well as radio-resistant, regulatory T cells inhibited antitumor immune response. In this study, C57/BL6 mice were administered 200 or 400 mg/kg of cyclophosphamide to deplete lymphocytes. On the same day, naive spleen T cells were transferred intravenously followed by subcutaneous injection of MCA205 tumor cells. We found that the percentage of regulatory T cells increased from 4-5% in normal mice to 16% in lymphopenic mice injected with cyclophosphamide. Transfer of naive T cells into cyclophosphamide injected lymphopenic mice showed some antitumor effects, and further elimination of regulatory T cells by anti-CD25 antibodies (PC61) following administration of cyclophosphamide significantly inhibited skin-tumor growth. It is well known that transforming growth factor-beta (TGF-beta) is critical differentiation cytokine for regulatory T cells. Thus, we examined the effects of anti-TGF-beta antibodies (1D11) on regulatory T cells during recovery from lymphopenia. Injection of anti-TGF-beta antibodies after lymphodepletion stimulated antitumor immune responses and delayed tumor progression.The results indicate that regulatory T cells are resistant to cytotoxic regimens. The combination of cytotoxic therapy and inhibition of regulatory T cells efficiently increases antitumor immune response.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1920." @default.
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- W2037701082 date "2010-04-15" @default.
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- W2037701082 title "Abstract 1920: Chemo-resistant regulatory T cells inhibit the augmentation of antitumor immunity during homeostatic T cell proliferation" @default.
- W2037701082 doi "https://doi.org/10.1158/1538-7445.am10-1920" @default.
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