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The gut microbiome affects response of treatments in HER2‐negative advanced gastric cancer

Authors :
Zihan Han
Siyuan Cheng
Die Dai
Yan Kou
Xiaotian Zhang
Fang Li
Xiaochen Yin
Jingjing Ji
Zhikuan Zhang
Xi Wang
Ning Zhu
Qi Zhang
Yan Tan
Xiaohuan Guo
Lin Shen
Zhi Peng
Source :
Clinical and Translational Medicine, Vol 13, Iss 7, Pp n/a-n/a (2023)
Publication Year :
2023
Publisher :
Wiley, 2023.

Abstract

Abstract Background Common treatments for metastatic/unresectable HER2‐negative gastric cancer include chemotherapy, immune checkpoint inhibitor monotherapy and chemotherapy plus immune checkpoint inhibitor. However, significant drug resistance exists regardless of the treatment regimen. Methods Patients with metastatic/unresectable HER2‐negative gastric/gastroesophageal junction adenocarcinoma were enrolled. All patients were divided into three groups according to the treatment regimen and were further divided into responders and non‐responders according to efficacy evaluation. Metagenomics sequencing were performed to analyze gut microbiome signature of patients receiving different treatments at baseline and throughout treatment. Results One hundred seventeen patients with HER2‐negative advanced gastric or gastroesophageal junction adenocarcinoma receiving chemotherapy alone, anti PD‐1/PD‐L1 immunotherapy alone or combined regimen were included in this study. Microbiome signatures related to clinical response are distinct among the three treatment groups. Among which, 14, 8 and 13 species were significantly different between responders and non‐responders in immunotherapy, immunotherapy plus chemotherapy and chemotherapy group, respectively. Patients with higher relative abundance of Lactobacillus possessed higher microbiome diversity and significantly better response to anti‐PD‐1/PD‐L1 immunotherapy and had a trend to achieve better progression‐free survival. Another cohort of 101 patients has been used as an external validation set to confirm the stability and reliability of these findings. Conclusions Gut microbiome affects response of treatments in HER2‐negative advanced gastric cancer in a treatment‐specific way, immunotherapy plus chemotherapy did not equal to a simple superposition of immunotherapy and chemotherapy. Lactobacillus is expected to become a novel choice as an adjuvant agent in promoting the efficacy of immunotherapy in gastric cancer.

Details

Language :
English
ISSN :
20011326
Volume :
13
Issue :
7
Database :
Directory of Open Access Journals
Journal :
Clinical and Translational Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.4f19acbb57394aceb79a009d42b067ff
Document Type :
article
Full Text :
https://doi.org/10.1002/ctm2.1312