Blueberry Extract Has Anti‐Proliferative Activity in Preclinical Models of Head and Neck Cancer

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) arises from premalignant lesions and has a high rate of disease relapse. Novel therapies are needed to treat established tumors and prevent progression of premalignant lesions. METHODS: Multiple immunocompetent murine models of oral cancer were used to explore the effects of blueberry extract (BE) on tumor control and anti-tumor immune responses. RESULTS: BE added to drinking water provided robust tumor growth delay, resulting in frequent tumor rejection when combined with anti-PD-1 immunotherapy in one model. Tumor immune profiling, RNA sequencing, and cell depletion studies suggest that BE acts primarily via non-immune, antioxidant mechanisms. When given to mice in the 4-NQO carcinogenesis model, BE showed modest activity as a chemoprevention strategy; in a model mimicking minimal residual disease, BE showed no appreciable benefit. CONCLUSIONS: These findings suggest that BE may have some utility as an adjunct to standard therapies for HNSCC, with limited utility during early tumorigenesis but more efficacy at later stages of tumor progression.