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In Vitro Assay to Study Tumor-macrophage Interaction
Published on: August 1, 2019
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IN VIVO STUDY OF POTENTIAL MECHANISMS OF MACROPHAGE REPOLARIZATION ON THE BACKGROUND OF TUMOR GROWTH
N Fedosova1, A Chumak1, N Cheremshenko1
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of the NAS of Ukraine, Kyiv, Ukraine.
Experimental Oncology
|June 9, 2024
Summary
Bacterial lectin from B. subtilis enhanced antitumor immunity in mice by preserving macrophage M1 polarization and boosting natural killer (NK) cell and cytotoxic T-lymphocyte activity. This suggests a role for STAT and IRF signaling pathways in immune response modulation.
Area of Science:
- Immunology
- Microbiology
- Oncology
Background:
- Peritoneal macrophages (Mph) play a crucial role in antitumor immunity, with M1 and M2 phenotypes exhibiting distinct functions.
- Tumor growth can lead to immunosuppression, often associated with M2 macrophage polarization and reduced effector cell activity.
- Bacterial lectins are being investigated for their immunomodulatory properties in cancer therapy.
Purpose of the Study:
- To investigate the effect of B. subtilis IMV B-7724 lectin on antitumor immunity effectors in a mouse model.
- To analyze the mechanisms of peritoneal Mph M1/M2 repolarization induced by bacterial lectin during tumor growth.
- To assess the impact of lectin administration on natural killer (NK) cells, cytotoxic T-lymphocytes (CTLs), and cytokine profiles.
Main Methods:
- Balb/c mice bearing Ehrlich adenocarcinoma (ACE) were treated with B. subtilis IMV B-7724 lectin (1 mg/kg, 10 doses).
- Immunological assessments included functional activity of Mph, NK cells, and CTLs, along with cytokine (IFN-γ, IL-4) levels.
- mRNA expression of STAT-1, STAT-6, IRF5, and IRF4 in Mph was evaluated to understand polarization mechanisms.
Main Results:
- Lectin administration preserved the M1 functional state of peritoneal Mph and maintained CD8+ T-lymphocyte cytotoxic activity.
- A significant increase in NK cell activity (2.7-fold vs. intact, 12.9-fold vs. untreated) was observed.
- Positive correlations were found between Mph/CD8+ T-lymphocyte activity, NO/Arg ratio, and antitumor effectiveness, indicating indirect Mph polarization via STAT and IRF pathways.
Conclusions:
- Bacterial lectin from B. subtilis can repolarize peritoneal Mph towards the M1 phenotype in ACE-bearing mice.
- This repolarization involves not only direct lectin-receptor interactions but also the activity of NK cells and T-lymphocytes.
- STAT and IRF signaling pathways are implicated in the lectin-induced Mph polarization process contributing to antitumor immunity.
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