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Novel targets for immune-checkpoint inhibition in cancer

Maxime Borgeaud1, Jose Sandoval1, Michel Obeid2

  • 1Geneva University Hospitals, Switzerland.

Cancer Treatment Reviews
|August 21, 2023
PubMed

Insights

Immune-checkpoint inhibitors are revolutionizing cancer therapy but face resistance. This review explores novel immune-checkpoint targets and resistance mechanisms to improve patient outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Therapy

Background:

  • Immune-checkpoint inhibitors (ICIs) have transformed cancer treatment.
  • However, many patients exhibit primary or acquired resistance to ICIs.
  • Mechanisms of resistance include intrinsic factors (e.g., neoantigen depletion) and extrinsic factors (e.g., T-cell exhaustion).

Purpose of the Study:

  • To analyze the evolving landscape of targetable immune-checkpoints in cancer.
  • To elucidate the biology of immune-checkpoints and their role in resistance.
  • To highlight promising strategies for overcoming ICI resistance.

Main Methods:

  • Review of current literature on immune-checkpoint biology and resistance.
  • Analysis of data from ongoing clinical trials investigating novel immune-checkpoints.
  • Synthesis of information on therapeutic strategies targeting immune-checkpoints.

Main Results:

  • Upregulation of PD-1, CTLA-4, and LAG-3 limits single-agent ICI efficacy.
  • Various intrinsic and extrinsic mechanisms contribute to ICI resistance.
  • Novel immune-checkpoint targets are under investigation to overcome resistance.

Conclusions:

  • Understanding immune-checkpoint biology is crucial for addressing resistance.
  • Targeting novel immune-checkpoints offers potential to improve ICI efficacy.
  • Ongoing clinical trials are vital for advancing cancer immunotherapy.
Keywords:
ICIICOSImmunotherapyLAG-3Novel immune-checkpoint inhibitor targetsNovel immune-checkpoint inhibitorsResistanceTIM-3VISTA

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