Abstract 2815: Sulindac reverses an immunosuppressive tumor microenvironment associated with obesity-driven metastatic mammary tumors in mice

Obesity is an established risk factor for several breast cancer (BC) subtypes. Obese BC patients also show poorer response to therapy, increased metastases, and increased mortality. While high levels of inflammation are thought to be a driver for BC metastasis, it is unknown how chronic exposure to low levels of obesity-associated inflammation contributes to BC progression and metastasis. We previously showed that treatment with the non-steroidal anti-inflammatory drug (NSAID) Sulindac (140 ppm mixed into control [10% kcal/fat] or diet induced obesity [DIO, 60% kcal/fat] diets) offset both the pro-growth and pro-metastatic effects of obesity on BC using three different mouse models of metastatic BC - basal-like E0771, and claudin-low metM-Wnt-lung and metM-Wnt-liver. To characterize the effect of Sulindac treatment on the tumor microenvironment, we conducted microarray analysis on E0771 tumors from mice in all four diet groups (Control, Control+Sulindac, DIO, and DIO+Sulindac). Ingenuity Pathway Analysis revealed significant Sulindac-induced differences (q Citation Format: Shannon B. McDonell, Alyssa J. Cozzo, Lydia K. Eisenbeis, Andrew J. Dannenberg, Stephen D. Hursting. Sulindac reverses an immunosuppressive tumor microenvironment associated with obesity-driven metastatic mammary tumors in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2815.