Soy-enriched diet limits tumor progression and reduces myeloid derived suppressor cells in the murine TRAMP model of prostate cancer.

Abstract

Abstract Epidemiological studies suggest diets enriched with soy confer a lower risk of prostate cancer. Data from our group and others indicate that soy has immunomodulatory properties which may contribute to their health promoting effects. Prior results from our group in a randomized phase II clinical trial revealed that men with asymptomatic prostate cancer on a soy-enriched diet had significantly reduced systemic inflammatory cytokines and myeloid-derived suppressor cells (MDSCs). We hypothesized that a soy-enriched diet limits systemic immunosuppression by reducing MDSC expansion. To understand how dietary soy modulates immune biomarkers in prostate cancer, we administered TRAMP (transgenic adenocarcinoma of the mouse prostate) mice a soy-enriched (n=28) or control diet (n=32) for 16 weeks. TRAMP mice administered a soy-enriched diet had a reduced tumor burden compared to control fed mice (p=0.0419). Splenic CD11b+Ly6GloLy6C− granulocytic (p=0.0195), CD11b+Ly6C+Ly6G− monocytic (p=0.0005), and total MDSCs (p=0.0009) were significantly reduced in TRAMP mice on a soy-enriched diet compared to control diet. However, we did not observe differences in circulating CD4+CD25+Foxp3+ T-regulatory cells or other circulating immune subsets such as CD4+ T cells, phenotypically defined T helper-1 (CD4+CXCR3+CCR4−CCR6−)/T helper-2 (CD4+CCR4+CXCR3+CCR6−) T cells, CD8+ T cells, and NK cells. Ongoing studies are examining plasma cytokine levels and immunosuppressive cell populations in the tumor microenvironment of mice from this study. Together, these data indicate that soy as a dietary natural product may have a modulatory effect during chemopreventive or immunotherapy in the setting of prostate cancer.