Abstract 162: Reduced pro-inflammatory cytokines and immunosuppressive cells in patients with prostate cancer following consumption of soy isoflavone enriched bread.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Soybeans are a rich source of bioactive phytochemcials. Among the phytochemicals, the isoflavones (primarily genistein and daidzein) have received the greatest attention regarding cancer prevention. Indeed, we and others have reported dietary soy has measureable benefit in experimental tumor models of prostate cancer (PCa). Thus, we and others are actively investigating the potential of diets rich in soy components to prevent or slow human PCa progression, particularly in the early hormone sensitive state. Isoflavones are hypothesized to act through various pathways to impact PCa progression, such as inhibition of tumor growth factor signaling, anti-angiogenesis, and cell cycle inhibition. However, one area that has received very little focus is the impact of soy components on the immune system. We hypothesized that dietary soy may benefit prostate cancer (PCa) patients by modulating the balance of pro-inflammatory cytokines and immunosuppressive cells. A randomized, phase II trial was conducted in 32 PCa patients with asymptomatic biochemical failure (rising prostate specific antigen/PSA). Patients were randomized to 3 slices of soy bread (33 mg isoflavones/slice) or soy bread containing almond extract daily as a source of β-glucosidase. Flow cytometry was used to study cellular phenotype and bioplex assay to measure cytokines in peripheral blood on days 0 (baseline) and 56. Soy isoflavone metabolites in patient urine were assessed by LC-MS/MS. Adequate blood samples were available from 25 of 32 men completing the >56 day protocol and evaluated. Phenotypic analysis of Day 0 and 56 blood revealed no change in percentage of CD8+ T cells, but showed increased CD56+ NK cells (p=0.038) and reduced CD4+ T cells (p=0.04). Cells with a natural T regulatory cell phenotype (CD4+CD25+FoxP3+) were significantly decreased after 56 days consuming either type of soy bread (p=0.035). A significant decrease in cells with a monocytic (CD33+HLADRlowCD14+) and granulocytic (CD33+HLADR-CD11b+) MDSC phenotype was observed in patients consuming both types of soy bread (p=0.0064 and p=0.049). Plasma cytokine and chemokine levels were significantly decreased on Day 56 compared to baseline. Subgroup analysis indicated reduction in both Th1 type cytokines (p=0.0349) and MDSC associated cytokines (p=0.0284). Th2 and Th17 cytokines were not significantly altered as compared to baseline. Exploratory analyses using a K-means clustering approach revealed patients who metabolized soy isoflavones into dihyrdodaidzein and equol had significantly lower MDSC after soy intervention (p's<0.02). Finally, patients with prolonged or no change in PSA doubling time had fewer T regulatory cells or MDSC on day 56 versus baseline. Our data suggests that soy bread modulates immune suppressor cell biology in humans and may enhance the efficacy of anti-cancer immune responses. Citation Format: Gregory Brian Lesinski, Thomas A. Mace, Patrick Reville, Jennifer Ahn-Jarvis, Matthew Bill, Courtney Nicholas, Yael Vodovotz, Elizabeth Grainger, Kenneth Riedl, Gregory Young, Steven Schwartz, Steven Clinton. Reduced pro-inflammatory cytokines and immunosuppressive cells in patients with prostate cancer following consumption of soy isoflavone enriched bread. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 162. doi:10.1158/1538-7445.AM2013-162