Reprogrammed in vitro M1 macrophages increases life expectancy of mice with Ehrlich ascites carcinoma

Abstract

Most tumors, especially malignant, engage the mechanisms of active reprogramming of macrophage from the
antitumor M1phenotype towards pro-tumoral M2 phenotype. M2 phenotype suppress anti-tumor immunity, promotes
growth and vascularization of tumor as well as invasion and metastasis of tumor cells. We hypothesized that
increasing the number of M1 macrophages in the tumor area may limit carcinogenesis and increase the lifespan
of an organism with a tumor. The purpose of this study was to experimental verification of this assumption on the
example of the most malignant type of tumor — Ehrlich ascites carcinoma (EAC). To achieve this goal, we fulfilled
three objectives: 1) evaluated the changes in phenotype of and secretory NO-producing activity of macrophages
in tumor development, 2) evaluated the effect of ascites on the phenotype and NO-producing secretory activity of
macrophages and 3) reprogrammed macrophages in vitro on M1 phenotype and evaluated the effect of these
macrophages on the life span of mice with EAC. Work was carried out on mice of C57BL/6J. Results showed that:
1) as the development of EAC dramatic inhibition of ability of macrophages to synthesize NO and reprogramming
M2 macrophage phenotype occurred; 2) ascitic fluid isolated from mice with tumor significantly inhibits a
NO-producing activity of macrophages; 3) introducing reprogrammed in vitro M1 macrophages in mice significantly
increased the resistance of these mice to the development of EAC in the parameters of life expectancy and
the accumulation of ascitic fluid in the abdominal cavity. Findings indicates a high prospect of the development of
new biotechnologies for limiting tumor growth by reprogramming in vitro macrophages.