Exp Mol Med.
2010 Jun;42(6):407-419. 10.3858/emm.2010.42.6.042.
Enhancement of antitumor effect using dendritic cells activated with natural killer cells in the presence of Toll-like receptor agonist
- Affiliations
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- 1Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeonnam 519-809, Korea. drjejung@chonnam.ac.kr
- 2Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju 501-757, Korea.
- 3Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju 501-757, Korea.
- 4Department of Microbiology, Chonnam National University Medical School, Gwangju 501-757, Korea.
- 5Department of Surgery, Chonnam National University Medical School, Gwangju 501-757, Korea.
- 6The Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University, Gwangju 500-757, Korea.
- 7Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806, Korea.
- KMID: 1078356
- DOI: http://doi.org/10.3858/emm.2010.42.6.042
Abstract
- Dendritic cells (DCs) play a role in natural killer (NK) cell activation, while NK cells are also able to activate and mature DCs. Toll-like receptors (TLRs) on the surface of DCs and NK cells induce the maturation and activation of these cells when engaged with their cognate ligand. We investigated to generate potent DCs by maturation with NK cells in the presence of TLR agonist in vitro and tested the efficacy of these DC vaccinations in mouse colon cancer model. The optimal ratios of DCs versus NK cells were 1:1 to 1:2. Immature DCs were mature with NK cells in the presence of lipopolysaccharide, which is TLR4 agonist, and further addition of IL-2 induced phenotypically and functionally mature bone marrow-derived DCs. These potent DCs exhibited not only high expression of several costimulatory molecules and high production of IL-12p40 and IL-12p70, but also high allogeneic T cells stimulatory capacity, and the induction of the high activities to generate tumor-specific CTLs. Consistently, vaccination with these DCs efficiently inhibited CT-26 tumor growth in mouse colon cancer model when compared to other vaccination strategies. Interestingly, combination therapy of these DC-based vaccines and with low-dose cyclophosphamide showed dramatic inhibition effects of tumor growth. These results suggest that the DCs maturated with NK cells in the presence of TLR agonist are potent inducer of antitumor immune responses in mouse model and may provide a new source of DC-based vaccines for the development of immunotherapy against colon cancer.
Keyword
MeSH Terms
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Animals
Cancer Vaccines/immunology/metabolism
Carcinoma/immunology/pathology/*therapy
Cell Line, Tumor
Cells, Cultured
Colonic Neoplasms/immunology/pathology/*therapy
Dendritic Cells/*drug effects/*immunology/transplantation
Female
Immunotherapy, Adoptive/*methods
Killer Cells, Natural/*immunology/physiology
Lipopolysaccharides/pharmacology
Mice
Mice, Inbred BALB C
Toll-Like Receptor 4/agonists
Toll-Like Receptors/*agonists
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