Related Experiment Video

Updated: Aug 14, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

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Transforming growth factor-β signalling in tumour resistance to the anti-PD-(L)1 therapy: Updated

Keywan Mortezaee1, Jamal Majidpoor2

  • 1Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Journal of Cellular and Molecular Medicine
|January 10, 2023
PubMed

Insights

Combining TGF-β inhibitors with immune checkpoint inhibitors (ICIs) shows promise for boosting anti-cancer immune responses. This strategy aims to overcome resistance to ICI therapy and improve durable responses in advanced cancers.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Biology

Background:

  • Immune checkpoint inhibitors (ICIs) show limited durable responses in many cancer patients.
  • Transforming growth factor-β (TGF-β) creates an immunosuppressive tumor microenvironment (TME), hindering ICI efficacy.
  • TGF-β signaling is linked to Programmed Death-Ligand 1 (PD-L1) expression, impacting anti-PD-1/PD-L1 therapy outcomes.

Purpose of the Study:

  • To explore strategies for enhancing anti-cancer immune responses beyond current ICI therapy.
  • To investigate the role of TGF-β in mediating resistance to ICI treatment.
  • To evaluate the potential of combining TGF-β inhibitors with anti-PD(L)1 therapies.

Main Methods:

  • Review of existing literature on TGF-β, TME, and ICI resistance mechanisms.
  • Analysis of studies investigating the interplay between TGF-β and PD-L1 expression.
  • Examination of preclinical and clinical data on combination therapies involving TGF-β inhibitors and anti-PD(L)1 agents.

Main Results:

  • TGF-β actively suppresses anti-tumor immunity within the TME.
  • Combined inhibition of TGF-β and PD-1/PD-L1 pathways demonstrates synergistic potential.
  • Development of bifunctional agents and fusion proteins targeting both TGF-β and PD-L1 is underway.

Conclusions:

  • Targeting TGF-β alongside PD-1/PD-L1 represents a promising strategy to overcome ICI resistance.
  • Combination therapies aim to reinvigorate immune responses for persistent anti-cancer effects.
  • This approach holds particular promise for treating "cold" tumors with limited immune infiltration.
Keywords:
immune checkpoint inhibitorprogrammed death-1 receptorprogrammed death-ligand 1resistancetransforming growth factor-βtumour microenvironment

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