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. 2024 Aug 7:15:1378900.
doi: 10.3389/fgene.2024.1378900. eCollection 2024.

Gut resistome of NSCLC patients treated with immunotherapy

Ewelina Iwan  1 , Anna Grenda  2 , Arkadiusz Bomba  1 , Katarzyna Bielińska  1 , Dariusz Wasyl  1 , Robert Kieszko  2 , Anna Rolska-Kopińska  2 , Izabela Chmielewska  2 , Paweł Krawczyk  2 , Kamila Rybczyńska-Tkaczyk  3 , Małgorzata Olejnik  4 , Janusz Milanowski  2
Affiliations

Gut resistome of NSCLC patients treated with immunotherapy

Ewelina Iwan et al. Front Genet. .

Abstract

Background: The newest method of treatment for patients with NSCLC (non-small cell lung cancer) is immunotherapy directed at the immune checkpoints PD-1 (Programmed Cell Death 1) and PD-L1 (Programmed Cell Death Ligand 1). PD-L1 is the only validated predictor factor for immunotherapy efficacy, but it is imperfect. Some patients do not benefit from immunotherapy and may develop primary or secondary resistance. This study aimed to assess the intestinal resistome composition of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors in the context of clinical features and potentially new prediction factors for assessing immunotherapy efficacy.

Methods: The study included 30 advanced NSCLC patients, 19 (57%) men and 11 (33%) women treated with first- or second-line immunotherapy (nivolumab, pembrolizumab or atezolizumab). We evaluated the patient's gut resistome composition using the high sensitivity of targeted metagenomics.

Results: Studies have shown that resistome richness is associated with clinical and demographic factors of NSCLC patients treated with immunotherapy. Smoking seems to be associated with an increased abundance of macrolides, lincosamides, streptogramins and vancomycin core resistome. The resistome of patients with progression disease appears to be more abundant and diverse, with significantly higher levels of genomic markers of resistance to lincosamides (lnuC). The resistance genes lnuC, msrD, ermG, aph(6), fosA were correlated with progression-free survival or/and overall survival, thus may be considered as factors potentially impacting the disease.

Conclusion: The results indicate that the intestinal resistome of NSCLC patients with immune checkpoint inhibitors treatment differs depending on the response to immunotherapy, with several distinguished markers. Since it might impact treatment efficacy, it must be examined more deeply.

Keywords: NSCLC; immunotherapy; metagenomics; microbiome; resistome.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Workflow of the experiment, including study groups, design of metagenomics analysis and resistome profiling.
FIGURE 2
FIGURE 2
The richness of ARG classes (A) in the group of patients with PFS below and above 6 months, (B) in the group of patients with progression disease (PD), stable disease (SD) and partial response (PR).
FIGURE 3
FIGURE 3
Kaplan-Meier survival curves of PFS for NSCLC patients treated with immunotherapy depending on (A) abundance of lnuC, (B) abundance of msrD.
FIGURE 4
FIGURE 4
Kaplan-Meier curves of overall survival curves of OS for NSCLC patients treated with immunotherapy depending on (A) abundance of ermG, (B) abundance of aph(6), (C) abundance of fosA, (D) abundance of msrD.
See this image and copyright information in PMC

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