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Updated: Mar 11, 2026
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
A clinic-responder-derived defined microbial consortium enhances anti-PD-1 immunotherapy efficacy in mice
Haiyan Zhou1, Ruiming Sun2,3, Xiaoqun Nie1
1State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Abstract:
Targeting the gut microbiota is a promising strategy to enhance the efficiency of cancer immunotherapy; however, success has been limited. Here we combined metagenomic analysis and in silico prediction to identify bacterial species associated with immunotherapy response in patients with non-small-cell lung cancer. We constructed a defined consortium (RCom) of 15 bacterial species, most of which were isolated from responder patient faeces, associated with improved clinical response to anti-programmed cell death protein 1 (PD-1) treatment. Metabolic models and in vitro experiments revealed that RCom is a stable and cooperative community, and in vivo experiments showed that RCom engrafts and produces immunomodulatory metabolites. Oral administration of RCom improved the anti-tumour activity of anti-PD-1 by increasing the intratumoural infiltration and cytotoxic function of CD8+ T cells in syngeneic tumour models and across mice with heterogeneity in baseline gut microbiota composition. RCom supplementation also limited anti-PD-1 resistance in mice conferred by faecal microbiota transplantation from individual non-responsive patients. These findings suggest that RCom is a potential adjuvant to improve responsiveness to anti-PD-1 therapy in cancer.
Insights
A novel bacterial consortium (RCom) enhances cancer immunotherapy. Oral RCom administration improved anti-programmed cell death protein 1 (PD-1) treatment efficacy by boosting anti-tumour immune responses.
Area of Science:
- Microbiome research
- Cancer immunotherapy
- Bacterial consortia
Background:
- Targeting the gut microbiota is a promising strategy for cancer immunotherapy.
- Current approaches have shown limited success in enhancing immunotherapy efficiency.
- Identifying specific bacterial species linked to treatment response is crucial.
Purpose of the Study:
- To identify bacterial species associated with immunotherapy response in non-small-cell lung cancer patients.
- To construct and evaluate a defined bacterial consortium for enhancing anti-programmed cell death protein 1 (PD-1) therapy.
Main Methods:
- Metagenomic analysis and in silico prediction to identify key bacterial species.
- Construction of a 15-species defined bacterial consortium (RCom) from responder patient samples.
- In vitro, in vivo, and syngeneic tumour model experiments to assess RCom's stability, engraftment, immunomodulatory effects, and anti-tumour activity.
Main Results:
- RCom demonstrated stability and cooperation within the community, producing immunomodulatory metabolites.
- Oral RCom administration enhanced anti-PD-1 therapy efficacy by increasing intratumoural CD8+ T cell infiltration and function.
- RCom supplementation reduced resistance to anti-PD-1 therapy in mouse models.
Conclusions:
- The defined bacterial consortium RCom shows potential as an adjuvant therapy.
- RCom can improve responsiveness to anti-PD-1 treatment in cancer patients.
- Further investigation into RCom's role in cancer immunotherapy is warranted.
