Gut microbial predictors of first-line immunotherapy efficacy in advanced NSCLC patients

Abstract

The composition of the gut microbiome of patients with advanced non-small cell lung cancer is currently considered a factor influencing the effectiveness of treatment with immune checkpoint inhibitors. We aimed to evaluate the baseline gut microbiome composition in patients before receiving first-line immunotherapy alone or combined with chemoimmunotherapy. We performed 16S rRNA sequencing based on hypervariable regions. Stool samples were collected from 52 patients with advanced NSCLC treated with immunotherapy or chemoimmunotherapy before treatment. We found that the Ruminococcaceae family, species Alistipes sp. genus Eubacterium ventriosum group and genus Marvinbryantia may be intestinal, microbiological predictors of response to treatment. Genus Akkermansia and species from the [Clostridum] leptum group predicted the length of PFS (progression-free survival). Longer OS (overall survival) is associated with bacteria from the Ruminococcaceae family genera [Eubacterium] ventriosum group, Marvinbryantia, Colidextribacter and species [Clostridum] leptum. Bacteria that have an adverse effect (shortening of PFS or OS) on the response to treatment using immune checkpoint inhibitors are Rothia genus, Streptococus salivarius, Streptococus, Family XIII AD3011 group and Family XIII AD3011 group, s. uncultured bacterium. The composition of intestinal flora can be a predictive factor for immunotherapy in NSCLC patients. Specific bacteria can be positively or negatively associated with response to treatment, progression-free survival, and overall survival. They can be potentially used as predictive markers in NSCLC patients treated with immunotherapy.

Keywords: 16S rRNA; Immunotherapy; Immunotherapy efficacy; Microbiome; NSCLC.

Fig. 1

Comparison of bacterial content (microbiome at the family level) between patients with NSCLC treated in the first-line ICI according to the observed disease response during the first months of treatment.

Fig. 2

Comparison of bacterial content (microbiome at species level) between NSCLC patients treated with first-line ICI according to observed clinical response during the first months of treatment.

Fig. 3

Comparison of bacterial content (microbiome at the family level) between NSCLC patients treated with first-line ICI according to PFS and OS length at 6- and 12-month intervals.

Fig. 4

Kaplan-Meier survival analysis curve in patients treated with ICI in the presence or absence of Micrococcaceae for PFS (a) and OS (c), Oscillospirales uncultured for PFS (b) and Gemellaceae for PFS (d).

Fig. 5

Comparison of bacterial content (microbiome at species level) in patients with PFS and OS at intervals below and above 6 and 12 months.

Fig. 6

Kaplan-Meier survival PFS analysis curve in patients treated with ICI in the presence or absence of genus Rothia for PFS (a), Alistipes sp. (b), Family XIII AD3011 group (c) and [Clostridium] leptum (d).