Fibroblasts Fuel Immune Escape in the Tumor Microenvironment

Trends Cancer. 2019 Nov;5(11):704-723. doi: 10.1016/j.trecan.2019.09.009. Epub 2019 Oct 29.

Abstract

Immune escape is central to the persistence of most, if not all, solid tumors and poses a critical obstacle to successful cancer (immuno)therapy. Cancer-associated fibroblasts (CAFs) constitute the most prevalent, yet heterogeneous, component of the tumor stroma, where they 'cool down' the immune microenvironment. The central role played by CAFs, both as a physical barrier and source of immunosuppressive molecules, sets them as a target to enhance immunotherapy of cancer. We outline the current understanding of how CAFs fuel immune escape, as well as their potential clinical applications. Whether these therapeutics really have clinically significant activity remains to be seen, but the outlook is positive.

Keywords: cancer modeling; cancer-associated fibroblasts; immune escape; immune system; immunotherapy; tumor microenvironment.

Publication types

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

MeSH terms

  • Cancer-Associated Fibroblasts / immunology*
  • Cancer-Associated Fibroblasts / pathology
  • Extracellular Matrix Proteins / immunology
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Immunotherapy / methods*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Tumor Escape / physiology*
  • Tumor Microenvironment / immunology*

Substances

  • Extracellular Matrix Proteins