Toll-like receptors (TLRs) in cancer; with an extensive focus on TLR agonists and antagonists

IUBMB Life. 2021 Jan;73(1):10-25. doi: 10.1002/iub.2412. Epub 2020 Nov 20.

Abstract

At the forefront of the battle against pathogens or any endogenously released molecules, toll-like receptors (TLRs) play an important role as the most noble pattern recognition receptors. The ability of these receptors in distinguishing "self" and "non-self" antigens is a cornerstone in the innate immunity system; however, misregulation links inflammatory responses to the development of human cancers. It has been known for some time that aberrant expression and regulation of TLRs not only endows cancer cells an opportunity to escape from the immune system but also supports them through enhancing proliferation and angiogenesis. Over the past decades, cancer research studies have witnessed a number of preclinical and clinical breakthroughs in the field of TLR modulators and some of the agents have exceptionally performed well in advanced clinical trials. In the present review, we have provided a comprehensive review of different TLR agonists and antagonists and discuss their limitations, toxicities, and challenges to outline their future incorporation in cancer treatment strategies.

Keywords: TLR agonists; TLR antagonists; cancer; inflammation; toll-like receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Immunity, Innate*
  • Immunotherapy / methods*
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Signal Transduction
  • Toll-Like Receptors / agonists*
  • Toll-Like Receptors / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Toll-Like Receptors