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Published on: June 2, 2023
Oat-β-glucan potentiates anti-PD-1 efficacy through Faecalibacterium prausnitzii-derived butyrate and
Shuaishuai Yang1, Haojie Lu1, Min Jin2
1Department of Epidemiology and Biostatistics, Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
Abstract:
The gut microbiota governs immune checkpoint blockade responses, yet actionable strategies remain scarce. Here, we report that oat-β-glucan enhances anti-PD-1 (programmed cell death protein 1) efficacy in murine models by selectively expanding Faecalibacterium prausnitzii (F. prausnitzii). Combining anti-PD-1 with either oat-β-glucan or F. prausnitzii boosts intratumoral dendritic cell and CD8+ T cell infiltration and cytotoxic activation compared with anti-PD-1 monotherapy. Metabolomics identifies F. prausnitzii-derived butyrate and indole-3-propionic acid (IPA) as key mediators. Mechanistically, butyrate activates dendritic cells via the histone deacetylase (HDAC)8/H3K27ac/nuclear factor κB (NF-κB) p65 pathway, while both butyrate and IPA potentiate CD8+ T cell effector responses. In our colorectal cancer cohort undergoing anti-PD-1 treatment, higher baseline F. prausnitzii abundance and elevated plasma butyrate and IPA correlate with improved responses, a signature corroborated in independent external cohorts. A human intervention study confirms oat-β-glucan's safety, its ability to increase butyrate and IPA, and its capacity to modulate F. prausnitzii. Collectively, our work uncovers a microbiota-metabolite-immune axis whereby oat-β-glucan primes tumors for immunotherapy sensitization.
Insights
Oat-β-glucan enhances immunotherapy by boosting the gut bacterium Faecalibacterium prausnitzii. This increases anti-tumor immune cell activity and improves responses in colorectal cancer patients.
Area of Science:
- Immunology
- Microbiology
- Oncology
Background:
- The gut microbiota significantly influences responses to immune checkpoint blockade therapies like anti-PD-1.
- Developing actionable strategies to modulate the microbiota for enhanced immunotherapy efficacy is crucial.
Purpose of the Study:
- To investigate whether oat-β-glucan can enhance anti-PD-1 therapy efficacy.
- To identify the mechanisms by which oat-β-glucan modulates the gut microbiota and anti-tumor immunity.
Main Methods:
- Utilized murine models treated with anti-PD-1, oat-β-glucan, or Faecalibacterium prausnitzii.
- Performed metabolomic analysis to identify key microbial metabolites.
- Assessed immune cell infiltration and activation within tumors.
- Analyzed a colorectal cancer patient cohort and conducted a human intervention study.
Main Results:
- Oat-β-glucan selectively expanded F. prausnitzii, enhancing anti-PD-1 efficacy.
- Combined therapy increased intratumoral dendritic cell and CD8+ T cell infiltration and activation.
- F. prausnitzii-derived metabolites, butyrate and indole-3-propionic acid (IPA), were identified as key mediators.
- Higher F. prausnitzii abundance and elevated butyrate/IPA correlated with better anti-PD-1 responses in patients.
- Human studies confirmed oat-β-glucan's safety and its ability to increase butyrate, IPA, and modulate F. prausnitzii.
Conclusions:
- Oat-β-glucan primes tumors for immunotherapy sensitization by modulating the gut microbiota-metabolite-immune axis.
- F. prausnitzii-derived butyrate and IPA enhance anti-tumor immunity through dendritic cell activation and CD8+ T cell potentiation.
- This highlights a novel therapeutic strategy combining dietary components with immune checkpoint inhibitors.
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