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Damage-associated molecular patterns and Toll-like receptors in the tumor immune microenvironment

Hideyuki Yanai1, Sho Hangai1, Tadatsugu Taniguchi1

  • 1Department of Inflammology, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.

International Immunology
|August 6, 2021
PubMed

Insights

Tumors create a protective tumor immune microenvironment (TIME) by evading immune surveillance. Understanding how damage-associated molecular patterns (DAMPs) and Toll-like receptors (TLRs) shape the TIME is key for developing new cancer immunotherapies.

Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Tumors evade immune surveillance, gaining a survival advantage.
  • The tumor immune microenvironment (TIME) is crucial for tumor survival.
  • Tumor-intrinsic factors, including soluble mediators, modulate immune cell function within the TIME.

Purpose of the Study:

  • To investigate how tumor-intrinsic mechanisms, specifically damage-associated molecular patterns (DAMPs) and Toll-like receptors (TLRs), influence the TIME.
  • To understand the role of DAMP-TLR interactions in shaping the TIME to promote tumor growth.
  • To identify potential new strategies for cancer immunotherapy based on these interactions.

Main Methods:

  • Characterization of soluble factors released by tumor cells.
  • Analysis of damage-associated molecular pattern (DAMP) molecules.
  • Investigation of Toll-like receptor (TLR) signaling pathways.
  • Assessment of immune cell modulation within the tumor microenvironment.

Main Results:

  • Tumor cells release DAMP molecules upon necrosis.
  • DAMPs are recognized by innate immune receptors like TLRs.
  • DAMP-TLR interactions stimulate immune cells within the TIME.
  • These interactions contribute to sculpting the TIME to favor tumor progression.

Conclusions:

  • DAMP-TLR interactions are critical in establishing a pro-tumorigenic TIME.
  • Targeting DAMP-TLR signaling pathways presents a promising avenue for cancer immunotherapy.
  • Further research into these mechanisms can lead to novel therapeutic strategies.
Keywords:
DAMPsTIMETLRtumor microenvironment

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