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Breaking the Invisible Barriers: Unleashing the Full Potential of Immune Checkpoint Inhibitors in Oncogene-Driven

Hoi-Hin Kwok1, Jiashuang Yang1, David Chi-Leung Lam1

  • 1Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Cancers
|June 22, 2023
PubMed

Insights

Targeted therapies and angiogenesis inhibitors improve outcomes for non-small cell lung cancer (NSCLC) but face resistance. Understanding the tumor immune microenvironment could expand the use of immune checkpoint inhibitors (ICIs) in lung adenocarcinoma (ADC).

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Targeted therapies like tyrosine kinase inhibitors (TKIs) offer improved outcomes and reduced toxicity for advanced non-small cell lung cancer (NSCLC) with specific genetic alterations (e.g., EGFR, ALK, ROS1).
  • Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) have also demonstrated increased overall survival (OS) in NSCLC patients.
  • Acquired resistance to targeted therapies presents a significant challenge for long-term treatment maintenance in lung adenocarcinoma (ADC).

Purpose of the Study:

  • To review current knowledge on the tumor immune microenvironment in lung ADC.
  • To discuss the dynamics of immune phenotypes relevant to treatment resistance.
  • To explore strategies for extending the applicability of immune checkpoint inhibitors (ICIs) in lung ADC patients who develop resistance to targeted therapies.

Main Methods:

  • Literature review of targeted therapies, angiogenesis inhibitors, and immune checkpoint inhibitors in NSCLC.
  • Analysis of studies investigating acquired resistance mechanisms.
  • Examination of research on tumor immune microenvironment and immune phenotypes.

Main Results:

  • While targeted therapies and VEGF inhibitors improve outcomes, acquired resistance limits their long-term efficacy.
  • Immune checkpoint inhibitors (ICIs) have transformed treatment for NSCLC lacking actionable mutations.
  • Current clinical data suggest no survival benefit from combining targeted therapy with ICIs.

Conclusions:

  • The tumor immune microenvironment and immune phenotypes are critical factors influencing treatment response and resistance in lung ADC.
  • Further research into these areas may identify new strategies to enhance the efficacy of ICIs in overcoming resistance to targeted therapies.
  • Understanding immune dynamics is key to expanding the use of ICIs for a broader range of lung ADC patients.
Keywords:
immune checkpoint inhibitornon-small cell lung cancertargeted therapytumor immune microenvironment

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