Roles of TGF-β signaling pathway in tumor microenvirionment and cancer therapy

Int Immunopharmacol. 2020 Dec;89(Pt B):107101. doi: 10.1016/j.intimp.2020.107101. Epub 2020 Oct 21.

Abstract

Transforming growth factor β (TGF- β) signaling pathway has pleiotropic effects on cell proliferation, differentiation, adhesion, senescence, and apoptosis. TGF-β can be widely produced by various immune or non-immune cells and regulate cell behaviors through autocrine and paracrine. It plays essential roles in biological processes including embryological development, immune response, and tumor progression. Few cell signalings can contribute to so many pleiotropic functions as the TGF- β signaling pathway in mammals. The significant function of TGF-β signaling in tumor progression and evasion leading it to draw great attention in scientific and clinical research. Understanding the mechanism of TGF- β signaling provides us with chances to potentiate the effectiveness and selectivity of this therapeutic method. Herein, we review the molecular and cellular mechanisms of TGF-β signaling in carcinomas and tumor microenvironment. Then, we enumerate main achievements of TGF-β blockades used or being evaluated in cancer therapy, providing us opportunities to improve therapeutical approaches in the tumor which thrive in a TGF-β-rich environment.

Keywords: Immune cells; TGF-β inhibitors; TGF-β signaling; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • RNA, Messenger / antagonists & inhibitors
  • Receptors, Transforming Growth Factor beta / antagonists & inhibitors
  • Signal Transduction* / drug effects
  • Signal Transduction* / immunology
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / metabolism*
  • Tumor Microenvironment / drug effects*
  • Tumor Microenvironment / immunology*

Substances

  • Immune Checkpoint Inhibitors
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta