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M3 Macrophages Stop Division of Tumor Cells In Vitro and Extend Survival of Mice with Ehrlich Ascites Carcinoma

Sergey Kalish, Svetlana Lyamina, Eugenia Manukhina, Yuri Malyshev, Anastasiya Raetskaya, Igor Malyshev

(Department of Pathophysiology, Moscow State University of Medicine and Dentistry n.a. A.I. Evdokimov, Moscow, Russian Federation)

Med Sci Monit Basic Res 2017; 23:8-19

DOI: 10.12659/MSMBR.902285

BACKGROUND: M1 macrophages target tumor cells. However, many tumors produce anti-inflammatory cytokines, which reprogram the anti-tumor M1 macrophages into the pro-tumor M2 macrophages. We have hypothesized that the problem of pro-tumor macrophage reprogramming could be solved by using a special M3 switch phenotype. The M3 macrophages, in contrast to the M1 macrophages, should respond to anti-inflammatory cytokines by increasing production of pro-inflammatory cytokines to retain its anti-tumor properties. Objectives of the study were to form an M3 switch phenotype in vitro and to evaluate the effect of M3 macrophages on growth of Ehrlich ascites carcinoma (EAC) in vitro and in vivo.
MATERIAL AND METHODS: Tumor growth was initiated by an intraperitoneal injection of EAC cells into C57BL/6J mice.
RESULTS: 1) The M3 switch phenotype can be programed by activation of M1-reprogramming pathways with simultaneous inhibition of the M2 phenotype transcription factors, STAT3, STAT6, and/or SMAD3. 2) M3 macrophages exerted an anti-tumor effect both in vitro and in vivo, which was superior to anti-tumor effects of cisplatin or M1 macrophages. 3) The anti-tumor effect of M3 macrophages was due to their anti-proliferative effect.
CONCLUSIONS: Development of new biotechnologies for restriction of tumor growth using in vitro reprogrammed M3 macrophages is very promising.

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