Milk fermented by Lactobacillus casei CRL431 improves host immune response in 4t1 breast cancer model and its metastasis

E. MENDEZ UTZ; A. DE MORENO DE LEBLANC; F. ARAGON; G. PERDIGON

Mar del Plata

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC) LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2016

Sociedad Argentina de Inmunología

Metastasis (MTS) from breast cancer is associated to high mortality rate. Despite the host immune response, tumor cells can stimulate the production of cytokines and growth factors to favour their growth and MTS. Previously, we reported that administration of milk fermented by Lactobacillus casei CRL431 (PFM) to mice bearing breast cancer diminished tumor growth, angiogenesis and lung MTS, and decreased the macrophages in mammary glands. The aim of this study was to evaluate the effect of PFM administration on immune cells in tumor and lungs, and to analyse systemic production of cytokines in a MTS model (without tumor presence). Mice were injected subcutaneously with 4T1 cells to induce primary tumors. When the tumors reached a volume of 1cm3, mice were randomly divided into 2 groups according they received PFM or milk. They were sacrificed after 30days and tumors were removed to isolate immune cells. For the study of MTS, tumors from other 10 mice (without special feeding) were surgically removed and mice were divided into 2 groups (PFM or milk). Mice were sacrificed after 70days; blood was collected for cytokine assays and lungs were removed to isolate immune cells. Immune cells from tumors and lung were analysed by flow cytometry. Like previous results, mice that received PFM decreased tumor growth. F4/80+cells showed decreased percentages in tumors from mice given PFM compared to milk group. PFM group showed the highest percentage of CD4/CD8 double-positive cells. In the MTS model, lungs from PFM group showed significant decreases in the percentage of F4/80+ cells compared to milk group. The analysis of cytokines in serum revealed that proinflammatory cytokines IL17, IL6 y TNFα were significantly diminished in PFM group compared to milk group. In conclusion, our results show that beneficial effects of PFM in mice bearing breast tumor and MTS was associated to changes on the host immune response, with diminution of macrophages and the pro-inflammatory environment