論文

国際誌
2015年7月15日

Critical Roles of Chemoresistant Effector and Regulatory T Cells in Antitumor Immunity after Lymphodepleting Chemotherapy.

Journal of immunology (Baltimore, Md. : 1950)
  • Yu Saida
  • ,
  • Satoshi Watanabe
  • ,
  • Tomohiro Tanaka
  • ,
  • Junko Baba
  • ,
  • Ko Sato
  • ,
  • Satoshi Shoji
  • ,
  • Natsue Igarashi
  • ,
  • Rie Kondo
  • ,
  • Masaaki Okajima
  • ,
  • Jun Koshio
  • ,
  • Kosuke Ichikawa
  • ,
  • Koichiro Nozaki
  • ,
  • Daisuke Ishikawa
  • ,
  • Toshiyuki Koya
  • ,
  • Satoru Miura
  • ,
  • Junta Tanaka
  • ,
  • Hiroshi Kagamu
  • ,
  • Hirohisa Yoshizawa
  • ,
  • Koh Nakata
  • ,
  • Ichiei Narita

195
2
開始ページ
726
終了ページ
35
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.4049/jimmunol.1401468

Antitumor immunity is augmented by cytotoxic lymphodepletion therapies. Adoptively transferred naive and effector T cells proliferate extensively and show enhanced antitumor effects in lymphopenic recipients. Although the impact of lymphodepletion on transferred donor T cells has been well evaluated, its influence on recipient T cells is largely unknown. The current study demonstrates that both regulatory T cells (Tregs) and effector CD8(+) T cells from lymphopenic recipients play critical roles in the development of antitumor immunity after lymphodepletion. Cyclophosphamide (CPA) treatment depleted lymphocytes more efficiently than other cytotoxic agents; however, the percentage of CD4(+)CD25(+) Foxp3(+) Tregs was significantly increased in CPA-treated lymphopenic mice. Depletion of these chemoresistant Tregs following CPA treatment and transfer of naive CD4(+) T cells augmented the antitumor immunity and significantly suppressed tumor progression. Further analyses revealed that recipient CD8(+) T cells were responsible for this augmentation. Using Rag2(-/-) mice or depletion of recipient CD8(+) T cells after CPA treatment abrogated the augmentation of antitumor effects in CPA-treated reconstituted mice. The transfer of donor CD4(+) T cells enhanced the proliferation of CD8(+) T cells and the priming of tumor-specific CD8(+) T cells originating from the lymphopenic recipients. These results highlight the importance of the recipient cells surviving cytotoxic regimens in cancer immunotherapies.

リンク情報
DOI
https://doi.org/10.4049/jimmunol.1401468
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26041539
ID情報
  • DOI : 10.4049/jimmunol.1401468
  • PubMed ID : 26041539

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