TGF-β: A novel predictor and target for anti-PD-1/PD-L1 therapy

Front Immunol. 2022 Dec 19:13:1061394. doi: 10.3389/fimmu.2022.1061394. eCollection 2022.

Abstract

Transforming growth factor-β (TGF-β) signaling regulates multiple physiological processes, such as cell proliferation, differentiation, immune homeostasis, and wound healing. Besides, TGF-β plays a vital role in diseases, including cancer. Accumulating evidence indicates that TGF-β controls the composition and behavior of immune components in the tumor microenvironment (TME). Advanced cancers leverage TGF-β to reshape the TME and escape immune surveillance. TGF-β-mediated immune evasion is an unfavorable factor for cancer immunotherapy, especially immune checkpoint inhibitors (ICI). Numerous preclinical and clinical studies have demonstrated that hyperactive TGF-β signaling is closely associated with ICI resistance. It has been validated that TGF-β blockade synergizes with ICI and overcomes treatment resistance. TGF-β-targeted therapies, including trap and bispecific antibodies, have shown immense potential for cancer immunotherapy. In this review, we summarized the predictive value of TGF-β signaling and the prospects of TGF-β-targeted therapies for cancer immunotherapy.

Keywords: PD-1; PD-L1; TGF-β; bispecific antibody; cancer biotherapy; cancer immunotherapy; tumor microenvironment.

Publication types

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

MeSH terms

  • B7-H1 Antigen
  • Humans
  • Immunotherapy
  • Neoplasms* / drug therapy
  • Neoplasms* / pathology
  • Signal Transduction
  • Transforming Growth Factor beta*
  • Tumor Microenvironment

Substances

  • Transforming Growth Factor beta
  • B7-H1 Antigen