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Inhibitory immune checkpoints in cancer immunotherapy

Zhenghai Tang1,2, André Veillette3,4,5

  • 1Cancer Center, Faculty of Health Sciences, University of Macau, Macau, SAR, China.

Science Immunology
|September 26, 2025
PubMed

Insights

Immune checkpoint inhibitors like PD-1 and CTLA-4 show variable cancer treatment efficacy. Further research is needed to understand complex mechanisms for developing safer and more effective immunotherapies.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Immune checkpoint inhibitors targeting PD-1 and CTLA-4 have revolutionized cancer therapy but exhibit limited efficacy in certain cancers.
  • Variable patient responses and emerging complexities necessitate exploration of additional immune checkpoints as therapeutic targets.

Purpose of the Study:

  • To review the complexities of inhibitory immune checkpoints beyond PD-1 and CTLA-4.
  • To provide insights for developing more effective and safer immunotherapies.

Main Methods:

  • Literature review of recent studies on immune checkpoint inhibitors.
  • Analysis of mechanisms of action and regulation of experimental inhibitory immune checkpoints.

Main Results:

  • Current immune checkpoint inhibitors have limitations in efficacy and patient variability.
  • Experimental checkpoints and their targeting drugs display unexpected or undesirable mechanisms of action.
  • Underappreciated complexities in immune checkpoint regulation impact therapeutic outcomes.

Conclusions:

  • A deeper understanding of immune checkpoint intricacies is crucial for advancing cancer immunotherapy.
  • Future therapeutic strategies must address these complexities to improve treatment effectiveness and safety.

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