title: M3 Macrophages Stop Division of Tumor Cells In Vitro and Extend Survival of Mice with Ehrlich Ascites Carcinoma.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Moscow State University of Medicine and Dentistry n.a. A.I. Evdokimov, Moscow, Russian Federation.
authors.forename: Sergey
authors.initials: S
authors.lastname: Kalish
authors.affiliation: Department of Pathophysiology, Moscow State University of Medicine and Dentistry n.a. A.I. Evdokimov, Moscow, Russian Federation.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Lyamina
authors.affiliation: Department of Stress and Adaptation, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation.|University of North Texas Health Science Center, Fort Worth, TX, USA.|South Ural State University Biomedical School, Chelyabinsk, Russian Federation.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Manukhina
authors.affiliation: Brookdale Hospital, Brooklyn, NY, USA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Malyshev
authors.affiliation: Department of Pathophysiology, Moscow State University of Medicine and Dentistry n.a. A.I. Evdokimov, Moscow, Russian Federation.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Raetskaya
authors.affiliation: Department of Pathophysiology, Moscow State University of Medicine and Dentistry n.a. A.I. Evdokimov, Moscow, Russian Federation.|Department of Stress and Adaptation, Institute of General Pathology and Pathophysiology, Moscow, Russian Federation.|University of North Texas Health Science Center, Fort Worth, TX, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Malyshev
mesh_terms: D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors; D050800:STAT6 Transcription Factor / Q000037:antagonists & inhibitors; D051900:Smad3 Protein / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D050796:STAT3 Transcription Factor; D050800:STAT6 Transcription Factor; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; C494087:Stat3 protein, mouse; C494100:Stat6 protein, mouse