Prevotellaceae Modulates Colorectal Cancer Immune Microenvironment to Assist Anti-PD-L1 Immunotherapy

Area of Science:

• Oncology
• Microbiome Research
• Immunotherapy

Background:

• Colorectal cancer (CRC) is a leading global cancer.
• Immunotherapy, particularly anti-PD-L1, shows promise in CRC treatment.
• Intestinal microbiota composition may impact anti-PD-L1 therapy efficacy.

Purpose of the Study:

• To investigate the link between intestinal bacteria and anti-PD-L1 therapy response in CRC.
• To explore the relationship between Prevotellaceae and immune-related genes in CRC.
• To validate the role of Prevotellaceae abundance in anti-PD-L1 efficacy through mouse models.

Main Methods:

• Bioinformatics analysis of CRC patient microbiota and immune infiltration.
• 16S rRNA sequencing for fecal Prevotellaceae abundance in mice.
• Flow cytometry, western blot, and qPCR to assess immune cell infiltration and cytokine levels (IFN-γ, IL-2, PD-L1) in tumor tissues.

Main Results:

• Significant differences in gut microbiota community evenness were observed between CRC patient subtypes.
• Prevotellaceae family members were enriched in a specific CRC subtype (cluster 3).
• In vivo experiments confirmed that Prevotellaceae abundance supports anti-PD-L1 immunotherapy efficacy.

Conclusions:

• Prevotellaceae facilitates anti-PD-L1 treatment in colorectal cancer.
• Elevating Prevotellaceae may enhance CRC immunotherapy.
• Findings provide a basis for developing improved CRC immunotherapeutic strategies.