Antitumor Effect of Apilactobacillus kosoi 10H by Inducing Immunostimulatory Macrophages

Abstract

Apilactobacillus kosoi (A. kosoi) 10H is a fructophilic lactic acid bacterium found in vegetable sugar fermentation liquid. It has been shown to possess high intestinal immunostimulatory activity. In this study, we investigated the potential for A. kosoi 10H heat-killed cells and their components to convert the phenotype of immunosuppressive M2 macrophages to immunostimulatory M1 macrophages. We further investigated the ability of induction of apoptosis of cancer cell lines by macrophage culture medium in the presence of A. kosoi 10H heat-killed cells. After induction of macrophage differentiation by phorbol 12-myristate 13-acetate in a THP-1 human monocyte–derived cell line, immunosuppressive M2 macrophages were induced by interleukin-6 (IL-6). When A. kosoi 10H heat-killed cells were brought into contact with IL-6-induced M2 macrophages, the expression of CD163 and CD209, which are M2 macrophage markers, markedly decreased, and the expression of CD80, human leukocyte antigen-DR isotype (HLA-DR), and tumor necrosis factor-α (TNF-α), markers of M1 macrophages, markedly increased. A similar effect was observed with a water-soluble extract and a hydrophobic liquid extract from A. kosoi 10H heat-killed cells. In addition, when M2 macrophage culture medium that had been conditioned with A. kosoi 10H heat-killed cells was added to the MCF-7 breast cancer cell line, we found that apoptosis was induced. TNF-α in the medium conditioned with macrophages cultured in the presence of A. kosoi 10H heat-killed cells was found to be partially responsible for MCF-7 cell death. This study presents basic data on the potential to use lactic acid bacteria to improve the cancer microenvironment.