2007年11月
OX40 ligand expressed by DCs costimulates NKT and CD4+ Th cell antitumor immunity in mice
JOURNAL OF CLINICAL INVESTIGATION
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- 巻
- 117
- 号
- 11
- 開始ページ
- 3330
- 終了ページ
- 3338
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1172/JCI32693
- 出版者・発行元
- AMER SOC CLINICAL INVESTIGATION INC
The exceptional immunostimulatory capacity of DCs makes them potential targets for investigation of cancer immunotherapeutics. We show here in mice that TNF-alpha-stimulated DC maturation was accompanied by increased expression of OX40 ligand (OX40L), the lack of which resulted in an inability of mature DCs to generate cellular antitumor immunity. Furthermore, intratumoral administration of DCs modified to express OX40L suppressed tumor growth through the generation of tumor-specific cytolytic T cell responses, which were mediated by CD4(+) T cells and NKT cells. In the tumors treated with OX40L-expressing DCs, the NKT cell population significantly increased and exhibited a substantial level of IFN-gamma production essential for antitumor immunity. Additional studies evaluating NKT cell activation status, in terms of IFN-gamma. production and CD69 expression, indicated that NKT cell activation by DCs presenting cc-galactosylceramide in the context of CD1d was potentiated by OX40 expression on NKT cells. These results show a critical role for OX40L on DCs, via binding to OX40 on NKT cells and CD4(+) T cells, in the induction of antitumor immunity in tumor-bearing mice.
- リンク情報
- ID情報
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- DOI : 10.1172/JCI32693
- ISSN : 0021-9738
- PubMed ID : 17975668
- Web of Science ID : WOS:000250676000025