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Gut resistome of NSCLC patients treated with immunotherapy

Ewelina Iwan1, Anna Grenda2, Arkadiusz Bomba1

  • 1Department of Omics Analyses, National Veterinary Research Institute, Pulawy, Poland.

Frontiers in Genetics
|August 22, 2024
PubMed
Abstract

Insights

The gut resistome composition differs in non-small cell lung cancer patients based on their response to immunotherapy. Specific resistance genes in the gut microbiome may predict treatment efficacy and patient survival outcomes.

Area of Science:

  • Oncology
  • Microbiome Research
  • Immunotherapy

Background:

  • Immunotherapy targeting Programmed Cell Death 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) is a key treatment for non-small cell lung cancer (NSCLC).
  • PD-L1 is an imperfect predictor of immunotherapy response, leading to primary or secondary resistance in some patients.
  • Understanding factors influencing immunotherapy efficacy is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the intestinal resistome composition in NSCLC patients undergoing immune checkpoint inhibitor therapy.
  • To correlate resistome profiles with clinical features and identify potential new predictors of immunotherapy efficacy.

Main Methods:

  • Targeted metagenomics was employed to analyze the gut resistome in 30 advanced NSCLC patients receiving immunotherapy (nivolumab, pembrolizumab, or atezolizumab).
  • Patients included 19 males and 11 females, treated with first- or second-line immunotherapy.

Main Results:

  • Resistome richness varied with clinical and demographic factors, including smoking history.
  • Patients with progressive disease exhibited a more abundant and diverse resistome, with higher levels of lincosamide resistance genes (e.g., *lnuC*).
  • Specific resistance genes (*lnuC*, *msrD*, *ermG*, *aph(6)*, *fosA*) correlated with progression-free and overall survival.

Conclusions:

  • The intestinal resistome composition differs significantly between NSCLC patients who respond to immunotherapy and those who do not.
  • Identified resistance markers suggest a potential role in predicting treatment efficacy and patient survival.
  • Further investigation into the gut resistome is warranted to optimize immunotherapy strategies for NSCLC.
Keywords:
NSCLCimmunotherapymetagenomicsmicrobiomeresistome

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