T-cell tumour exclusion and immunotherapy resistance: a role for CAF targeting

Br J Cancer. 2020 Oct;123(9):1353-1355. doi: 10.1038/s41416-020-1020-6. Epub 2020 Aug 24.

Abstract

Recent studies have highlighted a major role for cancer-associated fibroblasts (CAFs) in promoting immunotherapy resistance by excluding T cells from tumours. Recently, we showed that CAFs can be effectively targeted by inhibiting the enzyme NOX4; this 'normalises' CAFs and overcomes immunotherapy resistance. Here we discuss our study and other strategies for CAF targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cancer-Associated Fibroblasts / drug effects*
  • Cancer-Associated Fibroblasts / pathology
  • Cancer-Associated Fibroblasts / physiology
  • Drug Resistance, Neoplasm* / drug effects
  • Drug Synergism
  • Humans
  • Immunotherapy
  • Molecular Targeted Therapy / methods*
  • Molecular Targeted Therapy / trends
  • NADPH Oxidase 4 / antagonists & inhibitors
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Pyrazolones / administration & dosage
  • Pyrazolones / pharmacology*
  • Pyridones / administration & dosage
  • Pyridones / pharmacology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Antineoplastic Agents, Immunological
  • Pyrazolones
  • Pyridones
  • setanaxib
  • NADPH Oxidase 4
  • NOX4 protein, human