Enhancement of antitumor effect using dendritic cells activated with natural killer cells in the presence of Toll-like receptor agonist.
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.
Pham
Thanh Nhan Nguyen
TN
Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Jeonnam 519-809, Korea.
Hong
Cheol Yi
CY
Min
Jung-Joon
JJ
Rhee
Joon-Haeng
JH
Nguyen
Truc Anh Thi
TA
Park
Byoung Chul
BC
Yang
Deok-Hwan
DH
Park
Young-Kyu
YK
Kim
Hyeong-Rok
HR
Chung
Ik-Joo
IJ
Kim
Hyeoung-Joon
HJ
Lee
Je-Jung
JJ
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000378:metabolism; D002277:Carcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000637:transplantation; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D051197:Toll-Like Receptor 4 / Q000819:agonists; D051193:Toll-Like Receptors / Q000819:agonists*
D019496:Cancer Vaccines; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
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