Enhancement of antitumor effect using dendritic cells activated with natural killer cells in the presence of Toll-like receptor agonist

• Published in: Experimental & molecular medicine Vol. 42; no. 6; pp. 407 - 419
• Main Authors: Pham, Thanh Nhan Nguyen, Hong, Cheol Yi, Min, Jung-Joon, Rhee, Joon-Haeng, Nguyen, Truc-Anh Thi, Park, Byoung Chul, Yang, Deok-Hwan, Park, Young-Kyu, Kim, Hyeong-Rok, Chung, Ik-Joo, Kim, Hyeoung-Joon, Lee, Je-Jung
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2010; Springer Nature B.V; Korean Society for Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cancer Vaccines - immunology; Cancer Vaccines - metabolism; Carcinoma - immunology; Carcinoma - pathology; Carcinoma - therapy; Cell Line, Tumor; Cells, Cultured; Colonic Neoplasms - immunology; Colonic Neoplasms - pathology; Colonic Neoplasms - therapy; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - transplantation; Female; Immunotherapy, Adoptive - methods; Killer Cells, Natural - immunology; Killer Cells, Natural - physiology; Lipopolysaccharides - pharmacology; Medical Biochemistry; Mice; Mice, Inbred BALB C; Molecular Medicine; Original; Stem Cells; Toll-Like Receptor 4 - agonists; Toll-Like Receptors - agonists; 생화학; natural killer cells; dendritic cells; cancer vaccines; chemotherapy; immunotherapy; Toll-like receptor 4
• ISSN: 1226-3613; 2092-6413; 2092-6413
• DOI: 10.3858/emm.2010.42.6.042

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.