The gut microbiome affects response of treatments in HER2-negative advanced gastric cancer
Zihan Han1,2, Siyuan Cheng1,3, Die Dai4
1Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
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.
Insights
Gut microbiome impacts treatment response in HER2-negative gastric cancer differently based on therapy. Higher Lactobacillus abundance correlates with better response to immunotherapy, suggesting its potential as an adjuvant treatment.
Area of Science:
- Oncology
- Microbiome Research
- Gastroenterology
Background:
- Metastatic/unresectable HER2-negative gastric cancer treatments include chemotherapy and immunotherapy, but drug resistance is a significant challenge.
- Understanding factors influencing treatment efficacy is crucial for improving patient outcomes in advanced gastric cancer.
Purpose of the Study:
- To investigate the role of gut microbiome signatures in predicting treatment response in HER2-negative advanced gastric cancer.
- To analyze how gut microbiome composition differs among patients receiving chemotherapy, immunotherapy, or combination therapy.
Main Methods:
- Metagenomics sequencing was performed on 117 patients with HER2-negative advanced gastric/gastroesophageal junction adenocarcinoma receiving different treatment regimens.
- Patients were categorized into responders and non-responders based on treatment efficacy.
- Gut microbiome signatures were analyzed at baseline and throughout treatment, with findings validated in an independent cohort of 101 patients.
Main Results:
- Distinct gut microbiome signatures were associated with clinical response across chemotherapy, immunotherapy, and combination therapy groups.
- Specific microbial species differed significantly between responders and non-responders in each treatment group.
- A higher abundance of Lactobacillus was linked to increased microbiome diversity and significantly better response to anti-PD-1/PD-L1 immunotherapy, with a trend towards improved progression-free survival.
Conclusions:
- Gut microbiome influences treatment response in HER2-negative advanced gastric cancer in a treatment-specific manner.
- The combination of immunotherapy and chemotherapy does not simply equate to the additive effects of each modality.
- Lactobacillus shows promise as a novel adjuvant agent to enhance immunotherapy efficacy in gastric cancer treatment.
Related Concept Videos
01:50What is Monogastric Digestion?
01:16Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy
02:56Treatment Resistant Cancers
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...