TY - JOUR

T1 - The Macrophage Activator GcMAF-RF Enhances the Antitumor Effect of Karanahan Technology through Induction of M2-M1 Macrophage Reprogramming

AU - Ruzanova, Vera S

AU - Kirikovich, Svetlana S

AU - Levites, Evgeniy V

AU - Proskurina, Anastasia S

AU - Dolgova, Evgeniya V

AU - Ritter, Genrikh S

AU - Efremov, Yaroslav R

AU - Dubatolova, Tatyana D

AU - Sysoev, Alexander V

AU - Koleno, Danil I

AU - Ostanin, Alexandr A

AU - Chernykh, Elena R

AU - Bogachev, Sergey S

N1 - The authors express their gratitude to the Common Use Center of Flow Cytometry IC&G SB RAS, the CommonUse Center Vivarium for Conventional Animals IC&G SB RAS for providing mice. This research was funded by Inga N. Zaitseva, “ACTIVATOR MAF” LLC and the Russian Ministry of Science and High Education via the Institute of Cytology and Genetics (State Budget Project No. FWNR-2022-0016). Copyright © 2024 Vera S. Ruzanova et al.

PY - 2024

Y1 - 2024

N2 - Macrophages are the immune cells of high-immunological plasticity, which can exert both pro- and anti-inflammatory activity, as well as repolarize their phenotype to the opposite or neutral one. In this regard, M2 macrophages of the tumor-associated stroma (TAS) are a promising therapeutic target in treating malignant neoplasms. Using FACS assay, we have estimated the CD11b+/Ly-6G+/Ly-6C+ fraction of macrophages from the peritoneum and TAS in intact healthy mice and those with developed Lewis carcinoma, both untreated and treated according to Karanahan technology in combination with group-specific macrophage activator (GcMAF-RF). As well, the pattern of pro- and anti-inflammatory cytokines mRNA expression in different groups of experimental and tumor-bearing animals was assessed. It was found that: (i) exposure of intact mice to GcMAF-RF results in the increased number of CD11b+/Ly-6C+ peritoneal macrophages and, at the same time, the expression pattern of cytokines in peritoneal macrophages switches from that characteristic of the mixed M1/M2 phenotype to that characteristic of the neutral M0 one; (ii) combination of Karanahan technology and GcMAF-RF treatment results in M0/M1 repolarization of TAS macrophages; (iii) in tumor-bearing mice, the response of peritoneal macrophages to such a treatment is associated with the induction of anti-inflammatory reaction, which is opposite to that in TAS macrophages.

AB - Macrophages are the immune cells of high-immunological plasticity, which can exert both pro- and anti-inflammatory activity, as well as repolarize their phenotype to the opposite or neutral one. In this regard, M2 macrophages of the tumor-associated stroma (TAS) are a promising therapeutic target in treating malignant neoplasms. Using FACS assay, we have estimated the CD11b+/Ly-6G+/Ly-6C+ fraction of macrophages from the peritoneum and TAS in intact healthy mice and those with developed Lewis carcinoma, both untreated and treated according to Karanahan technology in combination with group-specific macrophage activator (GcMAF-RF). As well, the pattern of pro- and anti-inflammatory cytokines mRNA expression in different groups of experimental and tumor-bearing animals was assessed. It was found that: (i) exposure of intact mice to GcMAF-RF results in the increased number of CD11b+/Ly-6C+ peritoneal macrophages and, at the same time, the expression pattern of cytokines in peritoneal macrophages switches from that characteristic of the mixed M1/M2 phenotype to that characteristic of the neutral M0 one; (ii) combination of Karanahan technology and GcMAF-RF treatment results in M0/M1 repolarization of TAS macrophages; (iii) in tumor-bearing mice, the response of peritoneal macrophages to such a treatment is associated with the induction of anti-inflammatory reaction, which is opposite to that in TAS macrophages.

KW - Mice

KW - Animals

KW - Macrophages

KW - Macrophages, Peritoneal/metabolism

KW - Cytokines/metabolism

KW - Neoplasms/pathology

KW - Anti-Inflammatory Agents/metabolism

KW - Vitamin D-Binding Protein

KW - Macrophage-Activating Factors

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85187523661&origin=inward&txGid=6dd6b2a2b062025d6e0366b7dc87a343

U2 - 10.1155/2024/7484490

DO - 10.1155/2024/7484490

M3 - Article

C2 - 38455363

VL - 2024

JO - Journal of Immunology Research

JF - Journal of Immunology Research

SN - 2314-8861

M1 - 7484490

ER -