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Primary and Acquired Resistance against Immune Check Inhibitors in Non-Small Cell Lung Cancer

Qinying Sun1, Xiangzhen Wei2, Zhonglin Wang2

  • 1Department of Respiratory and Critical Care Medicine, Changhai Hospital, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200001, China.

Cancers
|July 27, 2022
PubMed

Insights

Immune checkpoint inhibitors (ICIs) show limited efficacy in advanced non-small cell lung cancer (NSCLC). This review explores resistance mechanisms and suggests strategies to improve ICI treatment outcomes for NSCLC patients.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Immune checkpoint inhibitors (ICIs) represent a significant advancement in treating advanced non-small cell lung cancer (NSCLC).
  • A substantial proportion of NSCLC patients (approximately 80%) exhibit primary or acquired resistance to ICIs, limiting their clinical benefit.
  • Understanding resistance mechanisms is crucial for improving therapeutic strategies in NSCLC.

Purpose of the Study:

  • To review and elucidate the multifaceted mechanisms underlying primary and acquired resistance to ICIs in NSCLC.
  • To explore potential predictive biomarkers for ICI response in NSCLC.
  • To discuss the role of the tumor microenvironment in ICI resistance and suggest novel therapeutic approaches.

Main Methods:

  • Comprehensive literature review of studies investigating ICI resistance in non-small cell lung cancer.
  • Analysis of reported mechanisms of primary and acquired resistance.
  • Synthesis of data on predictive biomarkers and tumor microenvironmental factors.

Main Results:

  • Detailed exposition of diverse mechanisms contributing to primary ICI resistance (lack of initial response) in NSCLC.
  • Explanation of mechanisms driving acquired ICI resistance (tumor relapse after initial response) in NSCLC.
  • Identification of emerging predictive biomarkers and key tumor microenvironmental features associated with ICI resistance.

Conclusions:

  • Resistance to ICIs remains a major challenge in advanced NSCLC, necessitating a deeper understanding of underlying biological processes.
  • Future research should focus on identifying reliable predictive biomarkers and targeting specific tumor microenvironmental components.
  • Developing novel treatment strategies that overcome ICI resistance is essential to improve patient outcomes in NSCLC.
Keywords:
immune check inhibitorsnon-small cell lung cancerprimary and acquired resistance

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