Targeted inhibition of IL-10-secreting CD25- Treg via p38 MAPK suppression in cancer immunotherapy

Kozo Ohkusu-Tsukada, Masahiro Toda, Heiichiro Udono, Yutaka Kawakami, Kimimasa Takahashi

研究成果: Article査読

24 被引用数 (Scopus)

抄録

Cancer-induced immunotolerance mediated by inducible Treg (iTreg) is a major obstacle to cancer immunotherapy. In a basic study of immunotolerance, injection of an endogenous superantigen, i.e. the minor lymphocyte stimulatory (Mls)-1a, into specific TCR Vβ8.1-Tg mice enabled generation of anergic CD25- iTreg, the immunosuppressive function of which was maintained by IL-10 production via p38-MAPK activation. Interestingly, although p38-chemical inhibitor (p38-inhibitor) is capable of breaking CD25- iTreg-induced immunotolerance, the p38-inhibitor had hardly any immunotolerance breaking effect when CD25+ Treg were present, suggesting that depletion of CD25+ Treg is necessary for p38-inhibitor to be effective. Peptide OVA323-339 iv.-injection into its specific TCR-Tg (OT-II) mice also induced adaptive tolerance by iTreg. Peptide immunotherapy with p38-inhibitor after CD25+ Treg-depletion was performed in an OVA-expressing lymphoma E.G7-bearing tolerant model established by adoptive transfer of OT-II CD25- iTreg, which resulted in suppression of tumor growth. Similarly, the antitumor immunity induced by peptide immunotherapy in colon carcinoma CT26-bearingmice, in which the number of IL-10-secreting iTreg is increased, was augmented by treatment with p38-inhibitor after CD25 + Treg-depletion and resulted in inhibition of tumor progression. These results suggest that simultaneous inhibition of two distinct Treg-functions may be important to the success of cancer immunotherapy.

本文言語English
ページ(範囲)1011-1021
ページ数11
ジャーナルEuropean Journal of Immunology
40
4
DOI
出版ステータスPublished - 2010 4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

フィンガープリント 「Targeted inhibition of IL-10-secreting CD25<sup>-</sup> Treg via p38 MAPK suppression in cancer immunotherapy」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル