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ORIGINAL RESEARCH article

Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1378900

Gut resistome of NSCLC patients treated with immunotherapy

Provisionally accepted
Ewelina Iwan Ewelina Iwan 1*Anna Grenda Anna Grenda 2*Arkadiusz Bomba Arkadiusz Bomba 1Katarzyna Bielińska Katarzyna Bielińska 1Dariusz Wasyl Dariusz Wasyl 1Robert Kieszko Robert Kieszko 2Anna Rolska-Kopińska Anna Rolska-Kopińska 2Izabela Chmielewska Izabela Chmielewska 2Paweł A. Krawczyk Paweł A. Krawczyk 2Kamila Rybczyńska-Tkaczyk Kamila Rybczyńska-Tkaczyk 3Małgorzata Olejnik Małgorzata Olejnik 4Janusz Milanowski Janusz Milanowski 2
  • 1 National Veterinary Research Institute (NVRI), Pulawy, Poland
  • 2 Medical University of Lublin, Lublin, Poland
  • 3 University of Life Sciences of Lublin, Lublin, Lublin Voivodeship, Poland
  • 4 Nicolaus Copernicus University in Toruń, Toruń, Pomeranian, Poland

The final, formatted version of the article will be published soon.

    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.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.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.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: resistome, microbiome, NSCLC, Immunotherapy, Metagenomics

    Received: 30 Jan 2024; Accepted: 16 Jul 2024.

    Copyright: © 2024 Iwan, Grenda, Bomba, Bielińska, Wasyl, Kieszko, Rolska-Kopińska, Chmielewska, Krawczyk, Rybczyńska-Tkaczyk, Olejnik and Milanowski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ewelina Iwan, National Veterinary Research Institute (NVRI), Pulawy, 24-100, Poland
    Anna Grenda, Medical University of Lublin, Lublin, Poland

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.