A. muciniphila augmented the efficacy of αPD-1 therapy against gastric tumours by driving CD8+ T-cell infiltration and activation and reshaping the intestinal microbiota.
Key Findings
Results
Combined treatment with A. muciniphila and αPD-1 significantly inhibited subcutaneous gastric tumour growth compared to individual treatments.
Statistical significance reached P < 0.0001 for tumour growth inhibition with combined treatment
A subcutaneous GC model was established in male strain 615 mice by inoculating 1 × 10^6 Mouse Forestomach Carcinoma (MFC) cells on Day 10
A. muciniphila was administered by daily oral gavage at 1 × 10^9 CFU per mouse from Day 0 to Day 31
αPD-1 antibody was administered intraperitoneally at 100 μg per mouse every 3 days from Day 16 to Day 31
Tumour volume was recorded every 3 days and tumours were collected on Day 31 for analysis
Results
Combined treatment with A. muciniphila and αPD-1 significantly promoted tumour cell apoptosis.
Tumour cell apoptosis was significantly increased with combined treatment (P < 0.0001)
Histological analyses were performed on tumours collected on Day 31
Apoptosis was assessed as part of histology analyses alongside flow cytometry and ELISA
Results
A. muciniphila increased the therapeutic effectiveness of αPD-1 treatment by driving CD8+ T-cell accumulation within the tumour microenvironment.
CD8+ T-cell accumulation within the TME was significantly increased (P < 0.0001)
CD8+ T-cell infiltration and activation were both driven by A. muciniphila supplementation
Flow cytometry was used to quantify immune cell populations within the tumour microenvironment
The effect on CD8+ T cells was identified as a key mechanism by which A. muciniphila augmented αPD-1 efficacy
Results
Supplementation with A. muciniphila reshaped the gut microbiota composition and was associated with a significant reduction in the relative abundance of Escherichia coli.
The relative abundance of Escherichia coli fell significantly with A. muciniphila supplementation (P = 0.0170)
Gut microbiota composition was assessed using 16S rRNA sequencing
A. muciniphila reshaped the 'leading constituents of the gut microbiota' according to the authors
Microbiota analysis was performed on samples collected on Day 31
Yang Z, Liang L, Li X, Peng X, Qian X, Huang Z, et al.. (2026). Akkermansia muciniphila enhances the antitumour efficacy of αPD-1 therapy in gastric cancer by remodelling the tumour immune microenvironment.. Toxicology and applied pharmacology. https://doi.org/10.1016/j.taap.2026.117711