Moscow State University of Medicine and Dentistry, Russian Federation
Malyshev Igor is a Head of the Department of Pathophysiology and Head of the Laboratory of Cell Biotechnology, Medical School at the Moscow State University of Medicine and Dentistry. He is the Head of the Laboratory of Stress, Institute of General Pathology and Pathophysiology, Moscow and Adjunct Professor of Biomedical Sciences, University of North Texas Health Science Center, USA. He is a Member of the board of directors of the International Society for Adaptive Medicine and an Editorial board member of Journal of Biosciences and Medicines. He has published 3 books and monographs and 146 full length articles.
Macrophages play a key role in the protumor transformation of immunity. Thus, macrophages are a very attractive target for pharmacology and biotechnology. We started developing a new cell biotechnology method for in vitro reprogramming of isolated macrophages towards an antitumor inverse phenotype, which will be resistant to protumor factors. Such reprogrammed macrophages administered back to the tumor might restrict the tumor growth. Our approach is based on ramification of the intracellular signaling pathway. For instance, the activation of macrophage TGF-β receptor results in the activation of Smad family transcription factors and subsequent production of anti-inflammatory, protumor cytokines. Simultaneously, TGF-β activates another transcription factor AP-1 and p38 that activates synthesis of proinflammatory, antitumor cytokines. Therefore, the inhibition of Smad or SARA may help developing a macrophage that responds to the action of protumor factors (TGF-β) by producing antitumor cytokines. Such a “smart” macrophage with inverse phenotype would not only prevent the protumor transformation of immunity but would additionally enhance the antitumor response. One can expect that the “smart” macrophage will follow the feedback principle: the more protumor factors the tumor produces, the more antitumor cytokines and immunity-activating factors the macrophage would produce. This principle would allow avoiding the excessive inflammation and tissue damage, which may occur if the macrophages overproducing proinflammatory cytokine are used. We have shown recently that administration of reprogrammed macrophages to mice with Erlich’s tumor almost doubled the mouse survival time.
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