Association between gut microbiome components and immunotherapy efficacy in two small cell lung cancer cases with divergent outcomes

Abstract

Introduction. Immunotherapy can be effective in some patients with small-cell lung cancer (SCLC) with goodperformance status. However, the factors contributing to sustained treatment responses remain unclear. Theintestinal microbiome profile has emerged as a potential biomarker for the effectiveness of chemoimmunotherapyin SCLC. Evidence suggests that microbiome diversity, both in richness and abundance, may influenceimmunotherapy outcomes. The presence or absence of specific bacterial populations may also be linked totreatment success or failure. This pilot study compared the gut microbiome profile in two SCLC patients withpartial responses to chemoimmunotherapy but had distinctly different outcomes.Material and methods. Metagenomic analysis of the gut microbiome was performed using stool samplesfrom two patients collected prior to treatment initiation. Gut microbiome composition was determined basedon next-generation sequencing of the hypervariable regions of the 16S rRNA gene. Both patients receiveda treatment regimen consisting of atezolizumab, carboplatin and etoposide.Results. The progression-free survival (PFS) and overall survival (OS) were 5.7 and 10.2 months for the firstpatient and 19.9 and 34.9 months for the second patient, respectively. The patient with early progressionexhibited reduced species-level diversity compared to the long-term responder. Additionally, bacteria fromthe families Lachnospiraceae, Akkermansiaceae were found to be more prevalent in the patient with greaterimmunotherapy benefit. Conversely, the families Enterobacteriaceae, Succinivibrionaceae, Streptococcaceae,and Desulfovibrionaceae were more abundant in the patient with short survival than in patients with prolongedresponse.Conclusions. Bacteria residing in the gut may affect the efficacy of chemoimmunotherapy in SCLC patientsand represents a promising candidate for predictive biomarkers of treatment response and efficacy