論文

国際誌
2012年9月20日

Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia.

Blood
  • Junko Baba
  • ,
  • Satoshi Watanabe
  • ,
  • Yu Saida
  • ,
  • Tomohiro Tanaka
  • ,
  • Takao Miyabayashi
  • ,
  • Jun Koshio
  • ,
  • Kosuke Ichikawa
  • ,
  • Koichiro Nozaki
  • ,
  • Toshiyuki Koya
  • ,
  • Katsuya Deguchi
  • ,
  • Chunrui Tan
  • ,
  • Satoru Miura
  • ,
  • Hiroshi Tanaka
  • ,
  • Junta Tanaka
  • ,
  • Hiroshi Kagamu
  • ,
  • Hirohisa Yoshizawa
  • ,
  • Ko Nakata
  • ,
  • Ichiei Narita

120
12
開始ページ
2417
終了ページ
27
記述言語
英語
掲載種別
研究論文(学術雑誌)

Cytotoxic lymphodepletion therapies augment antitumor immune responses. The generation and therapeutic efficacy of antitumor effector T cells (T(E)s) are enhanced during recovery from lymphopenia. Although the effects of lymphodepletion on naive T cells (T(N)s) and T(E)s have been studied extensively, the influence of lymphodepletion on suppressor cells remains poorly understood. In this study, we demonstrate a significant increase of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) in sublethally irradiated lymphopenic mice. These radio-resistant Tregs inhibited the induction of T(E)s in tumor-draining lymph-nodes (TDLNs) during recovery from lymphopenia. The transfer of T(N)s into lymphopenic tumor-bearing mice resulted in some antitumor effects; however, Treg depletion after whole-body irradiation and reconstitution strongly inhibited tumor progression. Further analyses revealed that tumor-specific T cells were primed from the transferred T(N)s, whereas the Tregs originated from irradiated recipient cells. As in irradiated lymphopenic mice, a high percentage of Tregs was observed in cyclophosphamide-treated lymphopenic mice. The inhibition of Tregs in cyclophosphamide-treated mice significantly reduced tumor growth. These results indicate that the Tregs that survive cytotoxic therapies suppress antitumor immunity during recovery from lymphopenia and suggest that approaches to deplete radio and chemo-resistant Tregs can enhance cancer immunotherapies.

リンク情報
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22806892
ID情報
  • eISSN : 1528-0020
  • PubMed ID : 22806892

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