REVIEW

Recent advances in the role of toll-like receptors and TLR agonists in immunotherapy for human glioma

  • Shuanglin Deng 1,2 ,
  • Shan Zhu 1 ,
  • Yuan Qiao 1 ,
  • Yong-Jun Liu 3 ,
  • Wei Chen 4 ,
  • Gang Zhao , 2 ,
  • Jingtao Chen , 1
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  • 1. Institute of Translational Medicine, the First Hospital, Jilin University, Changchun 130031, China
  • 2. Department of Neurosurgery, the First Hospital, Jilin University, Changchun 130031, China
  • 3. MedImmune, Gaithersburg, MD 20878, USA
  • 4. Department of Hematology-Oncology and BMT Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA

Received date: 25 Aug 2014

Accepted date: 30 Sep 2014

Published date: 30 Dec 2014

Copyright

2014 This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Gliomas are extremely aggressive brain tumors with a very poor prognosis. One of the more promising strategies for the treatment of human gliomas is targeted immunotherapy where antigens that are unique to the tumors are exploited to generate vaccines. The approach, however, is complicated by the fact that human gliomas escape immune surveillance by creating an immune suppressed microenvironment. In order to oppose the glioma imposed immune suppression, molecules and pathways involved in immune cell maturation, expansion, and migration are under intensive clinical investigation as adjuvant therapy. Toll-like receptors (TLRs) mediate many of these functions in immune cell types, and TLR agonists, thus, are currently primary candidate molecules to be used as important adjuvants in a variety of cancers. In animal models for glioma, TLR agonists have exhibited antitumor properties by facilitating antigen presentation and stimulating innate and adaptive immunity. In clinical trials, several TLR agonists have achieved survival benefit, and many more trials are recruiting or ongoing. However, a second complicating factor is that TLRs are also expressed on cancer cells where they can participate instead in a variety of tumor promoting activities including cell growth, proliferation, invasion, migration, and even stem cell maintenance. TLR agonists can, therefore, possibly play dual roles in tumor biology. Here, how TLRs and TLR agonists function in glioma biology and in anti-glioma therapies is summarized in an effort to provide a current picture of the sophisticated relationship of glioma with the immune system and the implications for immunotherapy.

Cite this article

Shuanglin Deng , Shan Zhu , Yuan Qiao , Yong-Jun Liu , Wei Chen , Gang Zhao , Jingtao Chen . Recent advances in the role of toll-like receptors and TLR agonists in immunotherapy for human glioma[J]. Protein & Cell, 2014 , 5(12) : 899 -911 . DOI: 10.1007/s13238-014-0112-6

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