| RRC ID |
45547
|
| 著者 |
Tomihara K, Kato K, Masuta Y, Nakamura K, Tanaka T, Hiratsuka H, Hamada H.
|
| タイトル |
Gene transfer of the CD40-ligand to human dendritic cells induces NK-mediated antitumor effects against human carcinoma cells.
|
| ジャーナル |
Int J Cancer
|
| Abstract |
The CD40-ligand (CD40L) is a key molecule for the activation of dendritic cells (DCs), followed by the induction of DC maturation and cytokine production. Here we found that DC infected with adenovirus vector encoding human CD40L (CD40L-DC) displayed significantly higher levels of immune accessory molecules and IL-12 production than did uninfected cells, and that CD40L-DC produced much higher levels of IFN-gamma. To investigate whether CD40L-DC-derived these soluble factors could stimulate NK cells without physical cell-to-cell contact, we cocultured NK cells with CD40L-DC in transwell culture plates. NK cells showed up-regulated cytotoxic activity toward various squamous oral cell carcinoma (OSC-70, HSC-2, HSC-3), and we determined that both IL-12 and IFN-gamma contributed to the CD40L-DC-mediated NK cell activation. NK cells stimulated with CD40L-DC resulted in the induction of the cell surface expression of TRAIL, the production of IFN-gamma and intracellular accumulation of granzyme B. The cytotoxic activity of NK cells stimulated with CD40L-DC could be mostly inhibited by neutralizing antibody for TRAIL and completely abrogated by the combination of antibody and exocytosis inhibitor, indicating that this was mainly mediated by a TRAIL-TRAIL-receptor interaction and granule exocytosis. Moreover, CD40L-DC-activated NK cells could induce up-regulation of a death-receptor TRAIL-R2 (DR5) and down-regulation of a decoy receptor TRAIL-R3 (DcR1) on carcinoma cells. Overall, these results have revealed that CD40L-DC could activate an innate immune reaction by stimulating NK cells followed by carcinoma cells, supporting that administration of CD40L-DC may have potential as an anticancer therapy.
|
| 巻・号 |
120(7)
|
| ページ |
1491-8
|
| 公開日 |
2007-4-1
|
| DOI |
10.1002/ijc.22518
|
| PMID |
17205529
|
| MeSH |
Adenoviridae / genetics
CD40 Ligand / genetics
CD40 Ligand / pharmacology*
Carcinoma, Squamous Cell / immunology
Carcinoma, Squamous Cell / secondary
Carcinoma, Squamous Cell / therapy*
Cytotoxicity, Immunologic
Dendritic Cells / cytology
Dendritic Cells / immunology*
Dendritic Cells / metabolism
Gene Transfer Techniques*
Genetic Therapy
Humans
Interferon-gamma / metabolism
Interleukin-12 / metabolism
Killer Cells, Natural / immunology*
Lymphocyte Activation
Mouth Neoplasms / immunology
Mouth Neoplasms / metabolism
Mouth Neoplasms / therapy*
Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
T-Lymphocytes, Cytotoxic
TNF-Related Apoptosis-Inducing Ligand / metabolism
Transfection
Tumor Cells, Cultured / immunology
Tumor Cells, Cultured / metabolism
Tumor Cells, Cultured / pathology
|
| IF |
5.145
|
| 引用数 |
15
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| 遺伝子材料 |
pCAhCD40L (RDB03915)
pWEAxCAhCD40L-FRGD (RDB03916)
AxCAhCD40L-FRGD (RDB03917). |
