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Interconnection of Gut Microbiome and Efficacy of Immune Checkpoint Inhibitors in Inoperable Non-Small-Cell Lung Cancer
Fedor Vladimirovich Moiseenko (Institute of Oncology NN Petrov, State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), Кечин Андрей Андреевич (Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences), Maksim Koryukov (Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences), U. A. Boyarskikh (Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences), Albina Gabina (Institute of Oncology NN Petrov, State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), A.P. Oganesian (Ministry of Health of the Russian Federation, State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), S.A. Belukhin (State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), М.Л. Макаркина (State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), Ekaterina Elsakova (State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), Elizaveta Artemeva (State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), A.V. Myslik (State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), Nikita Volkov (State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), Alexey A. Bogdanov (State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), Ekatherina Sh. Kuligina (Institute of Oncology NN Petrov, Ministry of Health of the Russian Federation), Светлана Николаевна Алексахина (Institute of Oncology NN Petrov), Aglaya G. Iyevleva (Institute of Oncology NN Petrov, Ministry of Health of the Russian Federation), Alexander O Ivantsov (Institute of Oncology NN Petrov, Ministry of Health of the Russian Federation), Andrey Bogdanov (State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care), Sidorenko Sv (Children's Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency, North-Western State Medical University named after I.I. Mechnikov), Гостев Владимир Валерьевич (Children's Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency, North-Western State Medical University named after I.I. Mechnikov), Aleksey S. Komissarov (Children's Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency, Federal Medical-Biological Agency), Дудурич Василиса Валерьевна, Lavrentii G. Danilov, Евгений Наумович Имянитов (Institute of Oncology NN Petrov, Ministry of Health of the Russian Federation), Vladimir Mikhailovich Moiseyenko (State Budget Institution of Health St. Petersburg Clinical Research Center Specialized Types of Medical Care)
Résumé : 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 (p-value = 0.0078 for the Chao1 index). Multiple specific taxa, such as Ruminococcus gauvreauii (p-value = 2 × 10−4), Ruminiclostridium 9 (p-value = 8 × 10−4), and [Eubacterium] ventriosum (p-value = 9 × 10−4), were enriched in patients with favorable outcomes, whereas Oscillibacter and the Eubacterium hallii group were associated with disease progression (p-value = 2 × 10−3 and 9 × 10−3, 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 (p-value = 9 × 10−7). 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.