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The Yin and Yang of Toll-like receptors in cancer

Abstract

Recognition of non-self molecular patterns by pattern recognition receptors is a cornerstone of innate immunity. Toll-like receptors (TLRs) exert a key role in recognizing pathogen-associated molecular patterns (PAMPs) but have also been implicated in the recognition of damage-associated molecular patterns (DAMPs). As such, TLRs regulate a wide range of biological responses including inflammatory and immune responses during carcinogenesis. The high expression of TLRs by antigen-presenting cells, including dendritic cells, and their ability to induce antitumor mediators such as type I interferon has led to efforts to utilize TLR agonists in tumor therapy in order to convert the often tolerant immune response toward antitumor responses. However, TLRs are also increasingly recognized as regulators of tumor-promoting inflammation and promoters of tumor survival signals. Here, we will review in detail the dichotomous role of TLRs in tumor biology, focusing on relevant TLR-dependent pro- and antitumor pathways, and discuss clinical applications of TLR-targeted therapies for tumor prevention and treatment.

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Acknowledgements

This work was supported by NIH grants U54CA163111, R01DK076920 and R01AA020211 (to RFS). Dianne H Dapito was supported by NIH grant F31DK091980.

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Correspondence to R F Schwabe.

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Pradere, JP., Dapito, D. & Schwabe, R. The Yin and Yang of Toll-like receptors in cancer. Oncogene 33, 3485–3495 (2014). https://doi.org/10.1038/onc.2013.302

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Keywords

  • MyD88
  • interleukin 6
  • tumor necrosis factor
  • NF-κB
  • Coley’s toxin
  • imiquimod

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