Isoflavones Reduced Anti-PD1 Response In Breast Cancer Models

06 Jul 20264 min read1 viewsJournal Feed

GIST (Key Takeaways)

Background. Fermentable dietary fibers, or microbiota-accessible carbohydrates (MACs), are hypothesized to enhance responsiveness to immune checkpoint blockade (ICB) therapy in breast cancer (BC) by increasing fecal short-chain fatty acid (SCFA) production. However, existing research findings have been inconsistent.
Given that hormone-sensitive breast cancer is highly influenced by estrogen levels, the presence of estrogenic isoflavones in certain MAC sources may partially account for these discrepancies. Consequently, investigating the roles of isoflavones versus MACs in BC models is warranted. Methods.
C57BL/6Tac mice were fed low-MAC (AIN93G), low-MAC supplemented with isoflavone genistein, high-MAC (5V5M), or high-MAC isoflavone (high-MACi; 5058D) diet to assess anti-PD1 efficacy against E0771 triple-negative breast cancer (TNBC) and 7,12-dimethylbenz[a]anthracene (DMBA)-initiated estrogen receptor α-positive (ERα+) mammary tumors. Effects of blocking ERα with tamoxifen (TAM) and dietary impact on the gut microbiome and immune signaling (NanoString) were also evaluated. Results.
High-MAC diets increased fecal microbial diversity, the abundances of SCFA-producing families, and fecal SCFA levels, compared with the low-MAC diet. Anti-PD1 was effective in TNBC models with high-MAC or low-MAC diets, but responsiveness was eliminated by the inclusion of isoflavones (high MACi) or genistein (low MAC).