1497P - Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in untreated advanced non-small-cell lung cancer

Background

Lung cancer is a malignancy with extremely high morbidity and mortality, of which non-small cell lung cancer (NSCLC) accounts for about 85%. With the advent of immunotherapy has brought survival benefit to NSCLC patients, some patients still be hard to achieving satisfactory outcomes. The link between gut microbes and immunotherapy is strong, but the role they play in NSCLC immunotherapy is unclear. The aim of this study was to investigate the relationship between gut microbial composition and the efficacy of immunotherapy in NSCLC.

Methods

Patients with advanced NSCLC receiving first-line immunotherapy were enrolled, and fresh stool samples were collected before and after 2 cycles of anti-PD-1 monoclonal antibody treatment for metagenomics sequencing and annotation using the KEGG and MetaCyc databases for subsequent differential flora analysis and functional analysis, and correlated the results with outcomes at 41 months.

Results

A total of 51 patients with advanced NSCLC treated with first-line immunotherapy were included in this study, and the relative abundance of Streptomyces, Corynebacterium, Kineosphaera, and Schaalia genus under the Actinomyces phylum was increased in the R group, and the PFS (progression-free survival time) of patients with high relative abundance of Schaalia and Corynebacterium genus was significantly longer than in those with low relative abundance. Functional analysis revealed reduced levels of glycolysis in the R group and may be due to the enrichment of Schaalia genus. The BMI and fasting glucose values of the patients may be influential factors in the relative abundance of Schaalia genus. In addition, the type of irAE occurrence was also correlated with the composition of gut microbes.

Conclusions

We have newly discovered that Schaalia genus under the Actinobacteria phylum may influence the efficacy of immunotherapy in NSCLC patients by inhibiting the level of glycolysis through affecting the level of PFP. Therefore, Schaalia flora may be a potential marker for predicting the efficacy of immunotherapy in NSCLC patients, and interfering with the levels of Schaalia or PFP is expected to be a new target to enhance the efficacy of immunotherapy in NSCLC patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.