Abstract 4951: Obesity-induced changes in baseline immune responses to pre-clinical breast cancer

Abstract

Abstract Obesity is known to increase morbidity and mortality in breast cancer patients; however, the immunological contributions to such changes remain incompletely understood. Our long-term goal is to investigate the broad impact of obesity on anti-tumor immunity, with a particular focus on understanding the mechanisms underlying obesity-induced immune alterations and how these alterations may influence the use of immunotherapeutics in breast cancer patients. For our studies, we utilized a diet-induced model of obesity (DIO) in which mice were fed either a high-fat or low-fat diet to generate DIO or age-matched lean controls, respectively. Animals were then challenged with the syngeneic E0771 mammary carcinoma cell line. Tumor outgrowth was quantified by caliper measurements, bioluminescent imaging (BLI) via firefly luciferase-expressing E0771 (E0771-fLUC) cells, and endpoint tumor weights. Whole tumor immunogenetic gene expression profiles were evaluated using nanoString and immune populations were assessed via multi-parameter flow cytometry. All measures of tumor outgrowth reveal that obesity significantly increases primary tumor outgrowth and induces a variety of alterations to the immunogenetic profile. Additionally, obesity significantly alters the frequency of intra-tumoral immune populations, including decreases in CD4+ and CD8+ T cells, increases in granulocytic myeloid-derived suppressor cells (G-MDSCs) and myeloid dendritic cells (mDCs), and a trending decrease in total CD45+ tumor infiltrating leukocytes. These alterations are specific to the tumor environment, as they are not present in the spleens of tumor-bearing mice. Collectively these data implicate obesity as a causal agent in impairing anti-tumor immune responses to murine mammary tumors. Furthermore, they suggest several cellular candidates for future mechanistic investigations into obesity-induced alterations in breast cancer immunity. Citation Format: Justin Gibson, Prabhakara Nagareddy, Lyse Norian. Obesity-induced changes in baseline immune responses to pre-clinical breast cancer [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 4951.