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Synergistical toll-like receptors activated dendritic cells induce antitumor effects against carcinoembryonic antigen-expressing colon cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

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.

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Acknowledgments

This work was supported by Science and Technology Commission of Shanghai Municipality (STCSM) grant 09411960700. We are grateful to Dr. Steven A. Rosenberg and Dr. John Shively for their generous providing of the cell lines and transgenic mice. We thank Dr. Xia Qin and Dr. Lili Wu for their expert technical help.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of General Surgery, Zhongshan Hospital, Fudan University, 180, Fenglin Road, Shanghai, China

    Xinqiang Hong, Tiangen Dong, Jianwei Hu, Tuo Yi, Wenxiang Li, Zhen Zhang, Shengli Lin & Weixin Niu

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  1. Xinqiang Hong
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  2. Tiangen Dong
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  3. Jianwei Hu
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  4. Tuo Yi
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  8. Weixin Niu
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Corresponding author

Correspondence to Weixin Niu.

Additional information

Hong XQ and Dong TG contributed equally to this paper.

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Hong, X., Dong, T., Hu, J. et al. Synergistical toll-like receptors activated dendritic cells induce antitumor effects against carcinoembryonic antigen-expressing colon cancer. Int J Colorectal Dis 28, 25–33 (2013). https://doi.org/10.1007/s00384-012-1530-7

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