EFFECT OF METRONOMIC CHEMOTHERAPY (MCT) WITH LOSARTAN (LOS) AND CYCLOPHOSPHAMIDE (CY) ON THE ANTI-TUMOR RESPONSE OF MACROPHAGES IN THE M-406 TRIPLE-NEGATIVE MAMMARY ADENOCARCINOMA MODEL IN FEMALE MICE WITH METABOLIC SYNDROME (MetS)

BARRANCO, MARIA MANUELA; HILLOTTE, GERALDINE; SCHAROVSKY O, GRACIELA; RICO, MARIA JOSE; ROZADOS, VIVIANA; GARCÍA, FABIANA; MAINETTI LEANDRO

MAR DE PLATA

Congreso; REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022; 2022

Breast cancer frequently coexists with Metabolic Syndrome (MetS), a pathology that is associated with cancer progression and a worse prognosis. Our aim was to evaluate the effect of MCT with CY+LOS on the anti-tumor response of macrophages, in mice with MetS bearing a mammary adenocarcinoma. CBi female mice (5 weeks) were fed with standard diet (SD) or diet with 40% calories of fat (HFD) throughout the experiment. At 20 weeks, the development of MetS was confirmed on the HFD group by biochemical and morphological parameters. Once the MetS features were settled, all mice were challenged orthotopically with M-406 tumor (day 0); when the tumor was palpable, mice of SD and HFD diets were distributed into 2 groups, GI: Control, with no treatment; GII: Cy 25mg/kg/day+Los 150mg/kg/day in the drinking water. Mice were weighted and tumor volume measured 3 times/week. When tumors were exponentially growing, mice were euthanized, tumors excised, fixed and paraffin included. Peritumoral and intratumoral macrophages [Total-Mt- (F4/80+), M1 (iNOS+, antitumoral) and M2 (MRC1+, protumoral)] were analyzed by immunofluorescence. GI-HFD mice showed a significantly higher number of Mt and M2 peritumoral macrophages compared to GI-SD mice (P