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Breakthroughs in immune checkpoint therapy: overcoming NSCLC immune checkpoint therapy resistance with novel

Li-Ping Kang1, Hua-Jing Huang2, Cong Xu3

  • 1Zhuhai Hospital of Integrated Traditional Chinese & Western Medicine, Zhuhai, Guangdong, China.

Frontiers in Immunology
|September 18, 2025
PubMed

Insights

Immune checkpoint therapy shows promise for non-small cell lung cancer (NSCLC) but faces resistance. This review explores new strategies like combination therapies and biomarkers to improve treatment effectiveness in cancer immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Research

Background:

  • Immune checkpoint therapy is a groundbreaking treatment for non-small cell lung cancer (NSCLC).
  • However, many patients develop resistance, limiting treatment efficacy.
  • Understanding resistance mechanisms is crucial for advancing cancer immunotherapy.

Purpose of the Study:

  • To provide a comprehensive review of immune checkpoint therapy in NSCLC.
  • To analyze current checkpoint inhibitors and resistance mechanisms.
  • To explore novel strategies for overcoming treatment resistance.

Main Methods:

  • Literature review of recent breakthroughs in immune checkpoint therapy.
  • Analysis of underlying biology, current inhibitors, and resistance mechanisms.
  • Exploration of novel strategies including combination therapies, neoantigen vaccines, and microbiome modulation.

Main Results:

  • Identified key mechanisms of primary and acquired resistance to immune checkpoint inhibitors.
  • Highlighted novel therapeutic strategies to overcome resistance.
  • Examined the role of biomarkers like TCR clonality and T-cell inflamed gene signatures in predicting response.

Conclusions:

  • Innovative approaches are needed to enhance the efficacy of immune checkpoint therapy in NSCLC.
  • Combination therapies, personalized vaccines, and microbiome modulation show potential.
  • Biomarker discovery is essential for predicting patient response and improving outcomes in cancer immunotherapy.
Keywords:
NSCLCT-cell inflamed gene signaturecombination immunotherapyepigenetic modifiersimmune checkpoint inhibitorsmicrobiome signaturespersonalized neoantigen vaccinesresistance mechanisms

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