"фараби əлемі" атты халықаралық ғылыми конференция материалдары
MYELOID DERIVED SUPPRESSOR CELLS INDUCED BY CHRONIC INFLAMMATION
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thesis114326
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MYELOID DERIVED SUPPRESSOR CELLS INDUCED BY CHRONIC INFLAMMATION FACILITATE TUMOR DEVELOPMENT Abdolla N, PerfilyevaY.V., TleulievaR., Krasnoshtanov V.K. 1 M.A.Aitkhozhin’s Institute of Molecular Biology and Biochemistry, Laboratory of Molecular Immunology and Immunobiotechnology, al-Farabi Kazakh National University nurshata@gmail.com Currently, an increase in the number of diseases associated with chronic inflammation, which result in decreased quality of life and increased death rates has been reported. According to the clinical and epidemiological data, chronic inflammation promotes development of at least 15-20% of all malignant neoplasms. Recent studies have demonstrated a critical role of myeloid derived suppressor cells (MDSCs) in cancer development. MDSCs are capable of creating an immunosuppressive microenvironment, which favors tumor progression. Under normal conditions, MDSCs are most commonly found in the bone marrow and in small amounts in the peripheral blood, but their numbers drastically increase during tumor development. A number of studies also reported an increased number of MDSCs in chronic inflammation. We hypothesized that MDSCs are involved in the process of chronic inflammation-mediated oncogenesis. Therefore, the purpose of this research was to study the effect of pharmacological correction of MDSCs in 87 combined models of chronic inflammation and transplanted tumors for the stimulation of antitumor immunity and subsequent tumor elimination. CD-1 male mice with body weights of 24-30- were used for the experiments. Adjuvant arthritis was induced by subcutaneous injection of complete Freund’s adjuvant into a hind limb footpad. Gemcitabine, antineoplastic drug, was administered intraperitoneally on the 7th, 10th days at the dose of 75 mg/kg. On the 14th day, 5x10 3 Ehrlich ascites carcinoma cells were inoculated subdermally. Mice were sacrificed on the 28th day, tumors were surgically removed and weighed, and flow cytometry analysis of splenic CD3, CD8, and MDSCs was performed. We observed a significantly increased tumor growth in mice with adjuvant-induced arthritis when compared to mice not subjected to chronic inflammation. Administration of gemcitabine resulted in a significantly reduced (p = 0.01) tumor growth in mice with chronic inflammation when compared with untreated mice. Immunophenotyping of splenocytes demonstrated that treatment with gemcitabine did not affect the number of CD3 and CD8 cells but significantly reduced accumulation of Ly6G - Ly6C + СD11b + M- MDSCs (p = 0,007) and production of reactive oxygen species (ROS) by Ly6G + Ly6C - СD11b - G-MDSCs (p = 0,003). Reduction of ROS production by G-MDSCs may be a result of an antioxidant effect of gemcitabine reported earlier. The results suggest that chronic inflammation promotes tumor growth through activation of immunosuppressive MDSCs and therapy of chronic inflammatory processes directed at MDSC elimination may be used for prevention of possible inflammation-related oncogenesis. Scientific Advisor: Doctor of Biology Science, Professor, Belyaev N.N жүктеу/скачать 2,79 Mb. Достарыңызбен бөлісу:
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