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Strategies to overcome resistance to immune checkpoint blockade in lung cancer

Ilaria Attili1, Paolo Tarantino2, Antonio Passaro1

  • 1Division of Thoracic Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Lung Cancer (Amsterdam, Netherlands)
|March 8, 2021
PubMed

Insights

Immune checkpoint inhibitors (ICIs) improve survival in non-small cell lung cancer (NSCLC), but resistance is common. Understanding resistance mechanisms is key to developing new strategies to overcome it and improve patient outcomes.

Area of Science:

  • Immunology
  • Oncology
  • Translational Medicine

Background:

  • Immune checkpoint inhibitors (ICIs) have revolutionized non-small cell lung cancer (NSCLC) treatment, offering long-term survival for some patients.
  • However, a significant challenge is the development of resistance to ICI therapy over time, limiting its efficacy.
  • This resistance is driven by complex factors including tumor cell-intrinsic changes and the tumor microenvironment.

Purpose of the Study:

  • To review the multifaceted mechanisms underlying resistance to immune checkpoint inhibitors in NSCLC.
  • To explore novel immune targets and strategies for overcoming ICI resistance.
  • To provide insights for future therapeutic development in NSCLC immunotherapy.

Main Methods:

  • Comprehensive literature review of studies on ICI resistance in NSCLC.
  • Analysis of tumor cell-intrinsic and tumor microenvironment factors contributing to resistance.
  • Identification and evaluation of alternative immune pathways and mediators for therapeutic intervention.

Main Results:

  • Multiple mechanisms contribute to ICI resistance, involving tumor genetics and the immune landscape.
  • Alternative immune receptors, pathways, and mediators represent potential targets for modulating immune responses.
  • Targeting these pathways may offer strategies to delay or prevent resistance development.

Conclusions:

  • A deeper understanding of ICI resistance mechanisms is crucial for advancing NSCLC treatment.
  • Identifying novel immune targets holds promise for developing next-generation immunotherapies.
  • Future research should focus on evaluating new strategies to overcome resistance and improve long-term patient survival.
Keywords:
Adoptive cell therapyGut microbiotaImmunotherapyResistance mechanismsTIGITTumour microenvironment

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