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Interleukin-22 promotes tumor angiogenesis.

Nicholas J Protopsaltis1, Wei Liang1, Eric Nudleman2

  • 1Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.

Angiogenesis
|December 13, 2018
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Summary

Interleukin-22 (IL-22), produced by T helper 17 (TH17) cells, promotes tumor angiogenesis by acting on endothelial cells. Blocking IL-22 inhibits tumor growth and reduces blood vessel formation.

Keywords:
AngiogenesisCytokineInflammationTumor

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Area of Science:

  • Immunology
  • Cancer Biology
  • Angiogenesis Research

Background:

  • T helper 17 (TH17) cells and their cytokine IL-17 are implicated in anti-VEGF therapy resistance.
  • TH17 cells recruit myeloid cells that support tumor growth and immunosuppression.

Purpose of the Study:

  • To investigate the role of IL-22, a TH17 effector cytokine, in tumor angiogenesis.
  • To determine if IL-22 can be a therapeutic target for inhibiting tumor growth.

Main Methods:

  • In vitro assays assessing endothelial cell proliferation, survival, and chemotaxis.
  • Ex vivo mouse choroid explant model for neovascularization.
  • In vivo tumor growth studies with IL-22 blockade using neutralizing antibodies.

Main Results:

  • IL-22 directly stimulates endothelial cell proliferation, survival, and migration.
  • IL-22 induces neovascularization in a mouse model.
  • Blockade of IL-22 significantly reduced tumor growth and tumor microvascular density.
  • IL-22 did not show synergistic effects with VEGF.

Conclusions:

  • IL-22 is a key mediator of tumor angiogenesis, acting directly on endothelial cells.
  • Targeting IL-22 represents a potential therapeutic strategy to inhibit tumor angiogenesis and growth.