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The gut microbiome and anti-PD1 immunotherapy
Immune checkpoint blockade (ICB) therapies are an emerging therapeutic option that aim to reinvigorate anti-tumour immune responses. ICB has been shown to be effective for some cancers when treated with anti-
PD1, however a large portion of patients do not respond favourably.Previous studies have hinted that the gut microbiota influences how well these therapies work, with the abundance of certain bacteria being linked to clinical outcomes. However, the precise ways these gut microbes activate the immune response in distant tumours were not fully understoodTo investigate this, researchers collected faecal samples from cancer patients undergoing PD-1 blockade therapy, categorising them as responders or non-responders.They found that patients who responded had an enrichment of bacteria belonging to the Ruminococcaceae family. From these responders' samples, they successfully isolated a previously unknown bacterial strain, YB328, belonging to the genus Hominenteromicrobium.Results Summary:
PD1, however a large portion of patients do not respond favourably.Previous studies have hinted that the gut microbiota influences how well these therapies work, with the abundance of certain bacteria being linked to clinical outcomes. However, the precise ways these gut microbes activate the immune response in distant tumours were not fully understoodTo investigate this, researchers collected faecal samples from cancer patients undergoing PD-1 blockade therapy, categorising them as responders or non-responders.They found that patients who responded had an enrichment of bacteria belonging to the Ruminococcaceae family. From these responders' samples, they successfully isolated a previously unknown bacterial strain, YB328, belonging to the genus Hominenteromicrobium.Results Summary:
- Faecal Microbiome Transplants from human responders enhanced the anti-tumour effects of PD-1 blockade in mice
- Administration of the YB328 alone did not inhibit tumour growth, but when combined with anti-PD-1 treatment, it significantly boosted anti-tumour efficacy across multiple mouse cancer models
- YB328 primarily activated CD103+CD11b− conventional dendritic cells (cDCs) in the gut which subsequently migrated to the tumour microenvironment to prime and activate CD8+ T cells
The findings suggest that boosting YB328 levels in patients, through direct administration of other microbiome interventions, could transform how we treat cancers, especially for patients who currently do not benefit from existing immune checkpoint therapies. For more information see:
https://www.nature.com/articles/s41586-025-09249-8
https://www.nature.com/articles/s41586-025-09249-8