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 mechanisms behind these changes remain unclear. The long-term goal of our study is to investigate the broad impact of obesity on anti-tumor immunity, with a particular focus on better understanding immune alterations that may influence the use of immunotherapeutics in breast cancer patients. We began by utilizing the leptin-deficient ob/ob mouse model of obesity and non-obese age matched C57BL/6 controls, in combination with the syngeneic E0771 mammary carcinoma cell line. Tumor outgrowth was quantified by means of caliper measurements, endpoint tumor weight, and bioluminescent imaging (BLI) via luciferase-expressing E0771 (E0771-fLUC) cells; immune cell populations were evaluated via multi-parameter flow cytometry. Primary and metastatic tumor growth were not significantly different between lean and ob/ob mice. In primary tumors, we found that obesity caused significant decreases in the frequencies of tumor-infiltrating granulocytic myeloid derived suppressor cells (G-MDSCs) and CD19+ B cells, and trending decreases in the frequencies of T (CD3+, CD4+, and CD8+) cells. In spleens, we found that both obesity and breast cancer induced a significant decrease in the frequency of dendritic and natural killer (NK) cell populations. Additionally, obesity induced a significant increase in the frequency of splenic monocytic myeloid-derived suppressor cells (M-MDSCs). Our findings suggest several cellular candidates for future mechanistic investigations into obesity-induced dysfunctions in breast cancer immunity.