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Current trends in sensitizing immune checkpoint inhibitors for cancer treatment

Jing Wei1, Wenke Li1, Pengfei Zhang1

  • 1Department of Medical Oncology, Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, China.

Molecular Cancer
|December 26, 2024
PubMed

Insights

Immune checkpoint inhibitors (ICIs) show promise in cancer treatment but face resistance. Understanding tumor biology and using combination strategies can overcome resistance and improve patient outcomes in cancer immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, offering significant clinical benefits for numerous malignancies.
  • However, resistance to immune checkpoint blockade (ICB) presents a major clinical hurdle, leading to inconsistent responses and limited long-term efficacy.
  • Tumor intrinsic and extrinsic factors contribute to this resistance, necessitating deeper investigation.

Purpose of the Study:

  • To review the biological mechanisms of ICIs and their resistance.
  • To explore the role of the tumor immune microenvironment (TIME) and predictive biomarkers.
  • To analyze current resistance mechanisms and propose combination strategies to enhance ICI effectiveness.

Main Methods:

  • Literature review focusing on ICI mechanisms, resistance pathways, and combination therapies.
  • Analysis of tumor biology, TIME components, and predictive biomarkers.
  • Synthesis of findings to outline strategies for overcoming ICI resistance.

Main Results:

  • ICIs have transformed cancer treatment but resistance remains a significant challenge.
  • Understanding tumor characteristics and the TIME is key to overcoming resistance.
  • Combination strategies, including personalized approaches, show potential to enhance ICI efficacy.

Conclusions:

  • Addressing ICI resistance requires a multifaceted approach, integrating knowledge of tumor biology and the immune microenvironment.
  • Predictive biomarkers are essential for patient stratification and treatment optimization.
  • Novel combination therapies hold promise for improving durable responses and extending clinical benefits in cancer immunotherapy.
Keywords:
Drug resistanceICIs sensitivityImmune checkpoint inhibitorsTME

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