title: Synergistical toll-like receptors activated dendritic cells induce antitumor effects against carcinoembryonic antigen-expressing colon cancer.
abstract: OBJECTIVE
  Dendritic cell (DC)-based cancer vaccine represents a promising immunotherapy against cancer. There has been recent evidence which have suggested that toll-like receptor (TLR) ligands may be critical for DC preparation; this was usually omitted in the past. Our study is designed to investigate if the vaccination of synergistical toll-like receptors activated DCs can induce more potent cytotoxic T Lymphocytes (CTL) responses and antitumor activity in carcinoembryonic antigen (CEA) transgenic mouse tumor models.
  
  
  METHODS
  We involved combination of TLR3 and TLR7/8 ligands in culture protocol of DCs. The DCs' surface molecules expression, IL-12 secretion and proliferation capacity of lymphocytes were tested. We also investigate the CTL activity against MC38-CEA colon tumor cells and the prophylactic and therapeutic effects of DC vaccination in subcutaneous mouse colon tumor models.
  
  
  RESULTS
  Compared with conventionally generated DCs, we showed synergistic TLR-activated DCs exhibited higher surface molecule expression, significantly higher secretion of IL-12 and more potent proliferating capacity of lymphocytes. Synergistic TLR-activated DCs were also able to induce lymphocytes possessing the specific cytotoxicity against MC38-CEA cells in vitro. Vaccination with CEA epitope pulsed TLR-activated DCs elicited antigen-specific preventive effect on MC38-CEA tumors, but failed to cure the tumor-bearing mice, that may be due to the suboptimal epitope selected and host immunosuppression.
  
  
  CONCLUSIONS
  Our results have proved that combined activation of TLRs can lead to better maturation status of DCs and also induce more effective antitumor immune responses against colon cancer, suggesting this may be a potential strategy to develop more powerful DC cancer vaccines.
authors: Department of General Surgery, Zhongshan Hospital, Fudan University, 180, Fenglin Road, Shanghai, China.
authors: Xinqiang
authors: X
authors: Hong
authors: Tiangen
authors: T
authors: Dong
authors: Jianwei
authors: J
authors: Hu
authors: Tuo
authors: T
authors: Yi
authors: Wenxiang
authors: W
authors: Li
authors: Zhen
authors: Z
authors: Zhang
authors: Shengli
authors: S
authors: Lin
authors: Weixin
authors: W
authors: Niu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D018664:Interleukin-12 / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019496:Cancer Vaccines; D002272:Carcinoembryonic Antigen; D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051193:Toll-Like Receptors; D018664:Interleukin-12