Immunotherapy with checkpoint inhibitors in non-small cell lung cancer: insights from long-term survivors

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1)-programmed cell death ligand-1 (PD-L1) axis are effective in non-small cell lung cancer (NSCLC).
• A subset of NSCLC patients exhibit persistent responses, forming a group of long-term survivors.
• Tumor PD-L1 expression, genomic landscape (mutational burden, neoantigens), and immune-related toxicities are associated with ICI response.

Purpose of the Study:

• To review the characteristics and clinical features of long-term NSCLC survivors.
• To identify potential biomarkers predictive of response to ICIs in NSCLC.
• To explore strategies for maximizing ICI efficacy through combination therapies.

Main Methods:

• Literature review focusing on long-term NSCLC survivors treated with ICIs.
• Analysis of studies correlating tumor characteristics (PD-L1 expression, genomics) with ICI response.
• Examination of research on immune-related toxicities as potential response indicators.

Main Results:

• Consistent association between PD-L1 expression and response in advanced NSCLC, despite variable definitions.
• Clinical efficacy of ICIs linked to tumor mutational burden and neoantigen load.
• Immune-related toxicities may correlate with improved immunotherapy response.

Conclusions:

• Understanding long-term survivor characteristics is crucial for optimizing ICI therapy in NSCLC.
• Biomarkers such as PD-L1 expression and genomic features are important for predicting ICI response.
• Combination strategies involving ICIs may enhance treatment efficacy and overcome resistance in NSCLC.