A natural polyphenol exerts antitumor activity and circumvents anti-PD-1 resistance through effects on the gut microbiota

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Representative immunofluorescence images of MCA-205 tumors for CD8+ , CD4+ and Foxp3+ cells in castalagin/IsoPD-1 and water/IsoPD-1 groups.

This interesting study conducted by Messaoudene et al. revealed a microbiota dependent anti-tumor activity in polyphenol-rich berry camu-camu.

Several approaches to manipulate the gut microbiome for improving the activity of cancer immune checkpoint inhibitors (ICI) are currently under evaluation. In this study they showed that the oral supplementation with the polyphenol-rich berry camu-camu in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response.

They identified the active compound in camu-camu castalagin, an ellagitannin:

Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/Foxp3+CD4+ ratio within the tumor microenvironment. Castalagin induced metabolic changes, resulting in an increase in taurine conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti-PD-1 activity. They found that castalagin binds to Ruminococcus bromii and promoted an anticancer response.

In conclusion, they reported that castalagin as a polyphenol that acts as a prebiotic to circumvent anti-PD-1 resistance.

This study and many more are to be presented in the 15th World Congress on Polyphenols Applications - on September 28-30, 2022 in Valencia, Spain. Stay tuned.

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