Interconnection of Gut Microbiome and Efficacy of Immune Checkpoint Inhibitors in Inoperable Non-Small-Cell Lung Cancer

The efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) varies widely across patients. Growing evidence indicates that the gut microbiome, through its interaction with the tumor microenvironment, may influence the response to immunotherapy. To investigate this, we analyzed fecal and tumor samples from 63 patients with inoperable NSCLC undergoing ICI therapy. Based on microbiome profiling using 16S rRNA sequencing, patients were grouped according to treatment benefit, defined as progression-free survival (PFS) of six months or longer. Associations between α-diversity indices, microbial composition at the genus and phylum levels, and a composite Sum Index of Binary Abundance (SIBA) were examined in relation to clinical outcomes. Higher microbial α-diversity was linked to improved response to ICIs (<i>p</i>-value = 0.0078 for the Chao1 index). Multiple specific taxa, such as <i>Ruminococcus gauvreauii</i> (<i>p</i>-value = 2 × 10<sup>-4</sup>), <i>Ruminiclostridium</i> 9 (<i>p</i>-value = 8 × 10<sup>-4</sup>), and [<i>Eubacterium</i>] <i>ventriosum</i> (<i>p</i>-value = 9 × 10<sup>-4</sup>), were enriched in patients with favorable outcomes, whereas <i>Oscillibacter</i> and the <i>Eubacterium hallii</i> group were associated with disease progression (<i>p</i>-value = 2 × 10<sup>-3</sup> and 9 × 10<sup>-3</sup>, respectively). The SIBA index, which reflects the absence of multiple beneficial bacterial taxa, proved to be a stronger predictor of treatment response than individual taxa alone. Median SIBA values were 18 vs. 24 in patients benefiting from IO therapy compared to non-responders (<i>p</i>-value = 9 × 10<sup>-7</sup>). These findings suggest that gut microbiome diversity and composition are closely tied to immunotherapy outcomes in NSCLC. Composite microbial metrics like SIBA may enhance predictive accuracy and inform personalized treatment approaches.

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Journal
International Journal of Molecular Sciences
Published
2025-08-11
DOI
https://doi.org/10.3390/ijms26167758
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
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article

Interconnection of Gut Microbiome and Efficacy of Immune Checkpoint Inhibitors in Inoperable Non-Small-Cell Lung Cancer

Andrey Kechin, Ekatherina Sh. Kuligina, Л. Г. Данилов, Maksim Koryukov et al.
International Journal of Molecular Sciences
Gut microbiota and health
article

Interconnection of Gut Microbiome and Efficacy of Immune Checkpoint Inhibitors in Inoperable Non-Small-Cell Lung Cancer

Andrey Kechin, Ekatherina Sh. Kuligina, Л. Г. Данилов, Maksim Koryukov, Alexey Bogdanov, Fedor Moiseenko, U. A. Boyarskikh, Maria Makarkina, Nikita Volkov, Vladimir Gostev, Евгений Наумович Имянитов, A.V. Myslik, Aleksey Komissarov, Aglaya G. Iyevleva, Elizaveta Artemeva, Ekaterina Elsakova, A.S. Zhabina, Светлана Николаевна Алексахина, S.A. Belukhin, Sidorenko Sv, V. V. Dudurich, Vladimir Moiseyenko, A.P. Oganesian, A.O. Ivantsov, Andrey Bogdanov
article en

Abstract

The efficacy of immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) varies widely across patients. Growing evidence indicates that the gut microbiome, through its interaction with the tumor microenvironment, may influence the response to immunotherapy. To investigate this, we analyzed fecal and tumor samples from 63 patients with inoperable NSCLC undergoing ICI therapy. Based on microbiome profiling using 16S rRNA sequencing, patients were grouped according to treatment benefit, defined as progression-free survival (PFS) of six months or longer. Associations between α-diversity indices, microbial composition at the genus and phylum levels, and a composite Sum Index of Binary Abundance (SIBA) were examined in relation to clinical outcomes. Higher microbial α-diversity was linked to improved response to ICIs (<i>p</i>-value = 0.0078 for the Chao1 index). Multiple specific taxa, such as <i>Ruminococcus gauvreauii</i> (<i>p</i>-value = 2 × 10<sup>-4</sup>), <i>Ruminiclostridium</i> 9 (<i>p</i>-value = 8 × 10<sup>-4</sup>), and [<i>Eubacterium</i>] <i>ventriosum</i> (<i>p</i>-value = 9 × 10<sup>-4</sup>), were enriched in patients with favorable outcomes, whereas <i>Oscillibacter</i> and the <i>Eubacterium hallii</i> group were associated with disease progression (<i>p</i>-value = 2 × 10<sup>-3</sup> and 9 × 10<sup>-3</sup>, respectively). The SIBA index, which reflects the absence of multiple beneficial bacterial taxa, proved to be a stronger predictor of treatment response than individual taxa alone. Median SIBA values were 18 vs. 24 in patients benefiting from IO therapy compared to non-responders (<i>p</i>-value = 9 × 10<sup>-7</sup>). These findings suggest that gut microbiome diversity and composition are closely tied to immunotherapy outcomes in NSCLC. Composite microbial metrics like SIBA may enhance predictive accuracy and inform personalized treatment approaches.

International Journal of Molecular SciencesVol. 26(16)
Institute of Chemical Biology and Fundamental Medicine (RU), Children's Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency (RU), Siberian Branch of the Russian Academy of Sciences (RU), Ministry of Health (MN), Institute of Problems of Mechanical Engineering (RU), State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care (RU), North-Western State Medical University named after I.I. Mechnikov (RU), Federal Medical-Biological Agency (RU), Saint Petersburg State Pediatric Medical University (RU)
Russian Science Foundation
Openalex Percentile: Top 82%
Gut microbiota and health
DOIOpen Access PDFOpenAlex
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