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Response to PD-1-Based Immunotherapy for Non-Small Cell Lung Cancer Altered by Gut Microbiota
Daqiang He1, Xing Li2, Rui An1
1Department of Laboratory Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang, China.
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.
Insights
Gut bacteria influence PD-1 immunotherapy response in non-small cell lung cancer (NSCLC). Specific bacteria like Escherichia-Shigella and Akkermansia correlate with better outcomes, suggesting their role in immunotherapy effectiveness.
Area of Science:
- Microbiome research
- Immunotherapy
- Oncology
Background:
- The human gut microbiota plays a role in cancer treatment efficacy.
- Understanding microbiota's impact on PD-1 immunotherapy for non-small cell lung cancer (NSCLC) is crucial.
Purpose of the Study:
- To identify specific gut bacteria influencing PD-1 immunotherapy outcomes in NSCLC patients.
- To explore the relationship between gut microbiota composition and immune responses.
Main Methods:
- 16S rRNA gene sequencing of fecal samples from advanced NSCLC patients undergoing PD-1 mAb therapy.
- Analysis of blood immune-related factors and gut microbiota diversity.
- Correlation analysis between microbial abundance and immune markers using Spearman's rank coefficient.
Main Results:
- Significant differences in gut microbiota diversity and composition were observed between patients with stable disease (SD) and progressive disease (PD).
- Higher abundance of Escherichia-Shigella, Akkermansia, and Olsenella was found in the SD group.
- Elevated levels of IL-12, IFN-γ, white blood cells, and specific immune cells (basophils, monocytes) were associated with the SD group and specific bacteria.
Conclusions:
- Gut microbiota composition significantly impacts PD-1 immunotherapy response in NSCLC patients.
- Escherichia-Shigella and Akkermansia show potential as key players in the efficacy of PD-1 inhibitory immunotherapy for NSCLC.
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