Gut Microbiota and Metabolites Associated with Immunotherapy Efficacy in Extensive-stage Small Cell Lung Cancer: a Pilot Study

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2024 Nov 18

PMID 39552845

Authors

Liyang Sun

Xueting Wang

Huimin Zhou

Rui Li

Ming Meng

Giandomenico Roviello

Byeongsang Oh

Lingxin Feng

Zhuang Yu

Jing Wang

Affiliations

Soon will be listed here.

Abstract

Background: The gut microbiota and its associated metabolites play a critical role in shaping the systemic immune response and influencing the efficacy of immunotherapy. In this study, patients with extensive-stage small cell lung cancer (ES-SCLC) were included to explore the correlation between gut microbiota and metabolites and immunotherapy efficacy in patients with ES-SCLC.

Methods: Pre- and post-treatment, we collected stool samples from 49 ES-SCLC patients treated with an anti-programmed death-ligand 1 (PD-L1) antibody. We then applied 16S ribosomal RNA (rRNA) sequencing and liquid chromatography-mass spectrometry (LC-MS) non-targeted metabolomics technology. Subsequently, the gut microbiota and metabolites were identified and classified.

Results: The results showed no statistical difference in gut microbiota alpha and beta diversity between the responder (R) and non-responder (NR) patients at baseline. However, the alpha diversity of the R patients was significantly higher than that of the NR patients after treatment. There were also differences in the microbiome composition at the baseline and post-treatment. Notably, after treatment, , , and were enriched in the R group, while , was enriched in the NR group. The non-targeted metabolomics results also indicated that short-chain fatty acids (SCFAs) were up-regulated in the R group after treatment. More, differential metabolites were enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the PD-L1 expression and programmed death 1 (PD-1) checkpoint pathway in cancer.

Conclusions: These findings are anticipated to provide novel markers for predicting the efficacy of immune checkpoint inhibitors (ICIs) in patients with ES-SCLC, and offer new directions for further research on molecular mechanisms.

Citing Articles

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Ciernikova S, Sevcikova A, Novisedlakova M, Mego M Cancers (Basel). 2025; 16(24.

PMID: 39766170 PMC: 11674129. DOI: 10.3390/cancers16244271.

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