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Mechanisms underlying response and resistance to immune checkpoint blockade in cancer immunotherapy

Junghwa Lee1, Eui Ho Kim1

  • 1Viral Immunology Laboratory, Institut Pasteur Korea, Seongnam, Republic of Korea.

Frontiers in Oncology
|August 24, 2023
PubMed

Insights

Immune checkpoint blockade (ICB) therapy shows promise but limited response rates in cancer. Understanding resistance mechanisms is key to improving efficacy and developing personalized combination treatments for more patients.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Immune checkpoint blockade (ICB) therapies targeting programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) have revolutionized cancer treatment.
  • However, a significant subset of patients do not respond to ICB therapy due to tumor and immune heterogeneity, exhibiting primary or acquired resistance.

Purpose of the Study:

  • To review the mechanisms of response and resistance to ICB, focusing on PD-1 and CTLA-4 pathways.
  • To explore strategies for overcoming resistance and designing personalized ICB-based combination regimens.

Main Methods:

  • Literature review of studies on immune checkpoint inhibitors (ICIs).
  • Analysis of mechanisms underlying anti-tumor immunity, response, and resistance to PD-1 and CTLA-4 blockade.
  • Exploration of potential biomarkers and combination therapies.

Main Results:

  • ICB efficacy is limited in many patients due to complex resistance mechanisms.
  • Understanding tumor immune evasion and heterogeneity is crucial for predicting response.
  • Various strategies are being investigated to enhance ICB effectiveness.

Conclusions:

  • Further research into ICB resistance mechanisms is essential to broaden clinical applicability.
  • Personalized combination regimens hold promise for improving patient outcomes in cancer immunotherapy.
  • Targeting PD-1 and CTLA-4 pathways requires a deeper understanding of anti-tumor immunity.
Keywords:
CTLA-4PD-1cancerimmune checkpoint blockaderesistanceresponse

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