ダウンロード数 : ?
ファイル
言語
英語
著者
頓宮 美樹 島根大学総合科学研究支援センター
原嶋 奈々江
門馬 浩行
稲尾 瞳子
内容記述(抄録等)
Several chemotherapeutic drugs have immune-modulating effects. For example, cyclophosphamide (CP) and gemcitabine (GEM) diminish immunosuppression by regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), respectively. Here, we show that intermittent (metronomic) chemotherapy with low-dose CP plus GEM can induce anti-tumor T cell immunity in CT26 colon carcinoma-bearing mice. Although no significant growth suppression was observed by injections of CP (100 mg/kg) at 8-day intervals or those of CP (50 mg/kg) at 4-day intervals, CP injection (100 mg/kg) increased the frequency of tumor peptide-specific T lymphocytes in draining lymph nodes, which was abolished by two injections of CP (50 mg/kg) at a 4-day interval. Alternatively, injection of GEM (50 mg/kg) was superior to that of GEM (100 mg/kg) in suppressing tumor growth in vivo, despite the smaller dose. When CT26-bearing mice were treated with low-dose (50 mg/kg) CP plus (50 mg/kg) GEM at 8-day intervals, tumor growth was suppressed without impairing T cell function; the effect was mainly T cell dependent. The metronomic combination chemotherapy cured one-third of CT26-bearing mice that acquired tumor-specific T cell immunity. The combination therapy decreased Foxp3 and arginase-1 mRNA levels but increased IFN-γ mRNA expression in tumor tissues. The percentages of tumor-infiltrating CD45^+ cells, especially Gr-1^<high> CD11b^+ MDSCs, were decreased. These results indicate that metronomic chemotherapy with low-dose CP plus GEM is a promising protocol to mitigate totally Treg- and MDSC-mediated immunosuppression and elicit anti-tumor T cell immunity in vivo.
主題
Cyclophosphamide
Gemcitabine
T cell immunity
MDSC
Treg
掲載誌名
Cancer Immunology and Immunotherapy
62
2
開始ページ
383
終了ページ
391
ISSN
03407004
発行日
2013-02
DOI
DOI公開日
2017-03-15
PubMed ID
NCID
AA00598499
出版者
Springer
資料タイプ
学術雑誌論文
ファイル形式
PDF
権利関係
© Springer-Verlag 2012
著者版/出版社版
著者版
業績ID
e22203
e20190
部局
研究・学術情報機構 総合科学研究支援センター
医学部
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