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18-10-2021 | Immunotherapy | Adis Journal Club | Article

Oncology and Therapy

Response to PD-1-Based Immunotherapy for Non-Small Cell Lung Cancer Altered by Gut Microbiota

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Authors: Daqiang He, Xing Li, Rui An, Lihong Wang, Yun Wang, Song Zheng, Xueqing Chen & Xianjun Wang

Abstract

Introduction

This study was designed to identify a group of bacteria in the human gut microbiota with specific effects on PD-1-based immunotherapy for patients with non-small cell lung cancer (NSCLC).

Methods

The study was performed in patients with advanced NSCLC, who received PD-1 monoclonal antibody (mAb) treatment for 6 months after one or several prior therapies. The combination of blood immune-related factors of the participants and their 16S rRNA gene sequencing from fecal samples at baseline was used to investigate the diversity and composition of the gut microbiota. The differences in relative abundance of gut microbiota at the genus level were compared, and the relation to blood immune-related factors was assessed using Spearman’s rank correlation coefficient analysis.

Results

The 16S rRNA gene sequencing showed a clear difference in the diversity and composition of the gut microbiota between groups with stable disease (SD) and progressive disease (PD). A comparison of differences in relative abundance at the genus level showed that the relative abundance of Escherichia-Shigella, Akkermansia and Olsenella in the SD group was significantly higher than that in the PD group. The SD group had significantly higher interleukin-12 (IL-12) and interferon γ (IFN-γ) levels than the PD group. Interestingly, the numbers of white blood cells and sorted cells in the SD group were higher than those in the PD group. Spearman’s rank correlation coefficient analysis showed that Escherichia-Shigella was positively correlated with IL-12, IFN-γ and basophils. Akkermansia was positively correlated with monocytes.

Conclusion

The response to PD-1-based immunotherapy in patients with NSCLC is affected by the diversity and composition of the gut microbiota. Escherichia-Shigella and Akkermansia may have specific effects on PD-1 inhibitory immunotherapy for NSCLC.

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Key Summary Points

Non-small cell lung cancer (NSCLC) patients with and without response to PD-I immunotherapy have different diversity and composition of gut microbiota.

The relative abundances of Escherichia-ShigellaAkkermansia and Olsenella might have contributed to the different composition of gut microbiota.

Escherichia-Shigella and Akkermansia might have specific effects on the PD-1 inhibitory immunotherapy for NSCLC, and a possible association with interleukin-12 (IL-12) and interferon gamma (IFN-γ).