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Isoflavones reduce the effectiveness of anti-PD1 treatment in breast cancer, independent of dietary fiber or fecal short-chain fatty acid concentrations
To investigate the roles of isoflavones versus microbiota-accessible carbohydrates (MACs) in breast cancer models and their impact on the effectiveness of anti-PD1 therapy.
Approach:
Dietary Intervention: C57BL/6Tac mice were fed different diets: low-MAC, low-MAC with isoflavone genistein, high-MAC, and high-MAC with isoflavones, to assess anti-PD1 efficacy against breast cancer.
Tumor Models: The study evaluated anti-PD1 efficacy in triple-negative breast cancer (TNBC) and estrogen receptor α-positive (ERα+) mammary tumors.
Tamoxifen Treatment: The effects of blocking ERα with tamoxifen (TAM) on anti-PD1 responsiveness were also assessed.
Key Findings:
High-MAC diets increased fecal microbial diversity and SCFA levels compared to low-MAC diets.
Anti-PD1 was effective in TNBC models with high-MAC or low-MAC diets, but responsiveness was eliminated by isoflavones.
Tamoxifen induced sensitivity to anti-PD1 in both TNBC and ERα+ models.
Interpretation:
Increased SCFA levels alone do not predict response to anti-PD1 therapy; the presence of isoflavones and ERα expression in tumors may impair treatment efficacy.
Limitations:
The study was conducted in murine models, which may not fully replicate human responses.
The specific mechanisms by which isoflavones affect immune response were not fully elucidated.
Conclusion:
Dietary components, particularly isoflavones, influence the effectiveness of immunotherapy in breast cancer.
by Fabia de Oliveira Andrade, Kerrie B. Bouker, Melike Ozgul-Onal, Lu Jin, Idalia Cruz, William Helferich, Audrey Gao, Karla Andrade de Oliveira, Vivek Verma, Christopher Staley, Patricia L. Foley, Leena Hilakivi-Clarke
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