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Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies
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T-cell tumour exclusion and immunotherapy resistance: a role for CAF targeting

Christopher J Hanley1,2, Gareth J Thomas3,4

  • 1School of Cancer Sciences, University of Southampton, Southampton, UK.

British Journal of Cancer
|August 25, 2020
PubMed

Insights

Cancer-associated fibroblasts (CAFs) hinder immunotherapy by blocking T cells. Inhibiting the NOX4 enzyme normalizes CAFs, overcoming this resistance and improving cancer treatment outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Biology

Background:

  • Cancer-associated fibroblasts (CAFs) are key players in the tumor microenvironment.
  • CAFs promote immunotherapy resistance by mediating T cell exclusion from tumors.

Purpose of the Study:

  • To discuss strategies for targeting CAFs to overcome immunotherapy resistance.
  • To highlight the role of NOX4 inhibition in normalizing CAFs and restoring anti-tumor immunity.

Main Methods:

  • Review of recent studies on CAF targeting.
  • Discussion of NOX4 inhibition as a therapeutic strategy.
  • Analysis of mechanisms underlying CAF-mediated T cell exclusion.

Main Results:

  • Targeting CAFs can overcome immunotherapy resistance.
  • Inhibition of NOX4 effectively normalizes CAFs.
  • Normalization of CAFs leads to T cell infiltration and improved immunotherapy response.

Conclusions:

  • NOX4 inhibition represents a promising strategy to enhance immunotherapy efficacy.
  • Targeting CAFs offers a viable approach to combat treatment resistance in cancer.
  • Further research into CAF-targeting therapies is warranted.

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