Toll-like receptors and immune regulation: implications for cancer therapy

Oncogene. 2008 Jan 7;27(2):181-9. doi: 10.1038/sj.onc.1210906.

Abstract

Toll-like receptors (TLRs) function as pathogen pattern recognition molecules that sensor and initiate innate and adaptive immune responses against microbes and cancer cells. Recognition of pathogen-derived ligands by TLRs expressed on many types of cells, including dendritic cells and T cells, triggers the nuclear factor (NF)-kappaB and type-1 interferon pathways, leading to the production of proinflammatory cytokines that are essential in stimulating CD4(+) T cells to differentiate to T helper (Th) 1, Th2 Th17 and regulatory T (Treg) cells. Recent studies indicate that Treg cells play a critical role in suppressing immune responses and inducing immune tolerance to cancer and infectious diseases. Of particular interest, the human TLR8 signaling pathway is essential for reversing the suppressive function of Treg cells. Thus, TLRs regulate cancer immunity and tolerance through innate immune responses mediated by Treg, dendritic and other immune cells. In this review, we focus on the current understanding of TLRs and Treg cells with emphasis on their roles in cancer immunity. Related information on non-TLR immune receptors will be briefly discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / physiology
  • Cell Differentiation / genetics
  • Gene Expression Profiling
  • Humans
  • Immunity / genetics
  • Immunity / physiology*
  • Inflammation / etiology
  • Inflammation / genetics
  • Inflammation / immunology
  • Ligands
  • Models, Biological
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / physiology
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism
  • Toll-Like Receptors / physiology*

Substances

  • Ligands
  • Toll-Like Receptors