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

作者: Hyeoung-Joon Kim , Je-Jung Lee , Thanh Nhan Nguyen Pham , Cheol Yi Hong , Jung-Joon Min

DOI: 10.3858/EMM.2010.42.6.042

关键词:

摘要: Dendritic cells (DCs) play a role in natural killer (NK) cell activation, while NK are also able to activate and mature DCs. Toll-like receptors (TLRs) on the surface of DCs induce maturation activation these when engaged with their cognate ligand. We investigated generate potent by presence TLR agonist vitro tested efficacy DC vaccinations mouse colon cancer model. The optimal ratios versus were 1:1 1:2. Immature lipopolysaccharide, which is TLR4 agonist, further addition IL-2 induced phenotypically functionally bone marrow-derived These exhibited not only high expression several costimulatory molecules production IL-12p40 IL-12p70, but allogeneic T stimulatory capacity, induction activities tumor-specific CTLs. Consistently, vaccination efficiently inhibited CT-26 tumor growth model compared other strategies. Interestingly, combination therapy DC-based vaccines low-dose cyclophosphamide showed dramatic inhibition effects growth. results suggest that maturated inducer antitumor immune responses may provide new source for development immunotherapy against cancer.

参考文章(38)
David Berd, Henry C. Maguire, Michael J. Mastrangelo, Potentiation of Human Cell-mediated and Humoral Immunity by Low-Dose Cyclophosphamide Cancer Research. ,vol. 44, pp. 5439- 5443 ,(1984)
Kerstin N. Schmidt, Beatrice Leung, Mandy Kwong, Kol A. Zarember, Sanjeev Satyal, Tony A. Navas, Fay Wang, Paul J. Godowski, APC-Independent Activation of NK Cells by the Toll-Like Receptor 3 Agonist Double-Stranded RNA The Journal of Immunology. ,vol. 172, pp. 138- 143 ,(2004) , 10.4049/JIMMUNOL.172.1.138
Orla M. Hart, Veronica Athie-Morales, Geraldine M. O’Connor, Clair M. Gardiner, TLR7/8-Mediated Activation of Human NK Cells Results in Accessory Cell-Dependent IFN-γ Production Journal of Immunology. ,vol. 175, pp. 1636- 1642 ,(2005) , 10.4049/JIMMUNOL.175.3.1636
Robbie B. Mailliard, Young-Ik Son, Richard Redlinger, Patrick T. Coates, Adam Giermasz, Penelope A. Morel, Walter J. Storkus, Pawel Kalinski, Dendritic cells mediate NK cell help for Th1 and CTL responses: two-signal requirement for the induction of NK cell helper function. Journal of Immunology. ,vol. 171, pp. 2366- 2373 ,(2003) , 10.4049/JIMMUNOL.171.5.2366
Lorenz Höltl, Reinhold Ramoner, Claudia Zelle-Rieser, Hubert Gander, Thomas Putz, Christine Papesh, Walter Nussbaumer, Claudia Falkensammer, Georg Bartsch, Martin Thurnher, Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide. Cancer Immunology, Immunotherapy. ,vol. 54, pp. 663- 670 ,(2005) , 10.1007/S00262-004-0629-2
Anick Chalifour, Pascale Jeannin, Jean-François Gauchat, Aline Blaecke, Martine Malissard, Thien N'Guyen, Nathalie Thieblemont, Yves Delneste, Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers α-defensin production Blood. ,vol. 104, pp. 1778- 1783 ,(2004) , 10.1182/BLOOD-2003-08-2820
Ji-Yan Liu, Yang Wu, Xiao-Shi Zhang, Jin-Liang Yang, Hong-Li Li, Yong-Qiu Mao, Yi Wang, Xia Cheng, Yong-Qiang Li, Jian-Chuan Xia, Maria Masucci, Yi-Xin Zeng, Single administration of low dose cyclophosphamide augments the antitumor effect of dendritic cell vaccine Cancer Immunology, Immunotherapy. ,vol. 56, pp. 1597- 1604 ,(2007) , 10.1007/S00262-007-0305-4
Daniel M. Andrews, Anthony A. Scalzo, Wayne M. Yokoyama, Mark J. Smyth, Mariapia A. Degli-Esposti, Functional interactions between dendritic cells and NK cells during viral infection Nature Immunology. ,vol. 4, pp. 175- 181 ,(2003) , 10.1038/NI880
Shinjiro Yamaguchi, Tomohide Tatsumi, Tetsuo Takehara, Ryotaro Sakamori, Akio Uemura, Tsunekazu Mizushima, Kazuyoshi Ohkawa, Walter J. Storkus, Norio Hayashi, Immunotherapy of murine colon cancer using receptor tyrosine kinase EphA2-derived peptide-pulsed dendritic cell vaccines Cancer. ,vol. 110, pp. 1469- 1477 ,(2007) , 10.1002/CNCR.22958