Cancer-associated fibroblasts: Key players in shaping the tumor immune microenvironment

Immunol Rev. 2021 Jul;302(1):241-258. doi: 10.1111/imr.12982. Epub 2021 Jun 1.

Abstract

Cancer immunotherapies have rapidly changed the therapeutic landscape for cancer. Nevertheless, most of the patients show innate or acquired resistance to these therapies. Studies conducted in recent years have highlighted an emerging role of cancer-associated fibroblasts (CAFs) in immune regulation that shapes the tumor immune microenvironment (TIME) and influences response to cancer immunotherapies. In this review, we outline recent advances in the understanding of phenotypic and functional heterogeneity of CAFs. We will focus on emerging roles of CAFs in shaping the TIME, especially under a framework of tumor immunity continuum, and discuss current and future CAF-targeting therapeutic strategies in particular in the context of optimizing the success of immunotherapies.

Keywords: TGF beta; cancer-associated fibroblast; immune-desert; immune-excluded; immune-infiltrated; tumor-immune phenotype.

Publication types

  • Review

MeSH terms

  • Cancer-Associated Fibroblasts*
  • Humans
  • Immunotherapy
  • Neoplasms* / therapy
  • Tumor Microenvironment