Abstract 3691: Fish oil increases immune cell infiltration of tumors and reduces the incidence of mammary carcinogenesis in Her2neu mice.
Authors: Turbitt William J. , Collins Shawntawnee D. , Xu Haifang , Washington Sharlene , Aliaga Cesar , El-Bayoumy Karam , Manni Andrea , Rogers Connie J. 
Published: August 2014

The role of omega-3 fatty acids (n-3 FA) in breast cancer prevention is widely studied, however much controversy exists in the field. In numerous preclinical models including the Her2neu transgenic model, consumption of n-3 FA provides a protective effect in mammary carcinogenesis. However, to date few studies have explored the effect of n-3 FA supplementation on immune modulation and if such changes contribute to the cancer prevention effects of n-3 FA. The goal of the current study was to explore the role of fish oil, as the source of n-3 FA, on immune markers and tumor yield in a Her2/neu transgenic model. Her2neu mice were randomized to two dietary interventions: AIN-93G-based diet with 1) 11% of diet (per gram weight) as corn oil (CO) or 2) 10% of diet as menhaden fish oil plus 1% of diet as corn oil (FO) (n=30/gr). FO significantly reduced the incidence and multiplicity of tumors in Her2neu mice (P&lt;0.05). A cohort of mice (n=10/gr) were sacrificed at 4 months just prior to developing focal malignant mammary lesions. No differences in the size or cellularity of the spleen were observed; however flow cytometric analysis revealed that FO mice had a significantly greater number of several cell types (CD3+ T cells, NK1.1+ NK cells, CD11c+ DCs) and a greater number of splenic Gr1+/CD11b+ cells than CO mice (14.3 ± 2.6 X 106 vs. 3.6 ± 1.8 X106, respectively; P&lt;0.05). Gr1+/CD11b+ cells are markers that define myeloid derived suppressor cells (MDSCs) which increase with tumor growth and have immunosuppressive function. However, recent reports have documented a role for MDSCs in immune modulation and the emergence of MDSCs subtypes that have different functional roles. A second cohort of mice (n=10/gr) were sacrificed at 12-15 months when ∼80% of control mice have been shown to develop mammary tumors. FO mice had significantly larger spleens with greater splenocyte counts than CO mice (270.3 ± 69.3 X106 and 198.9 ± 38.7 X 106, respectively; P&lt;0.05), which was comprised of a greater number of most cells types (CD3+, F480+, CD11c+, and NK1.1+ cells) including splenic Gr-1+/CD11b+ MDSCs (13.1 ± 4.6 X 106 and 3.4 ± 1.8 X106, respectively P&lt;0.05). Despite the presence of more Gr1+/CD11b+ cells in the spleens of FO mice, T cells from these mice had significantly greater IL-2 and IFN- γ release in response to in vitro stimulation with anti-CD3 (0.5 μg/ml), suggesting that Gr1+/CD11b+ cells may not be inhibiting T cell function in FO mice. Lastly, FO mice had a greater number of tumor infiltrating immune cells than CO mice, including CD3+, NK1.1+, F480+ and Gr1+/CD11b+ cells (P&lt;0.05). The presence of a greater number of tumor infiltrating immune cells correlates with reduced tumor burden in the FO mice. These data suggest unique immune modulatory effects of FO in tumor-bearing animals. This work is supported by the Susan G. Komen Foundation, Komen Grant KG0681632.

Citation Format: William J. Turbitt, Shawntawnee D. Collins, Haifang Xu, Sharlene Washington, Cesar Aliaga, Karam El-Bayoumy, Andrea Manni, Connie J. Rogers. Fish oil increases immune cell infiltration of tumors and reduces the incidence of mammary carcinogenesis in Her2neu mice. [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 3691. doi:10.1158/1538-7445.AM2013-3691