Study On Changes Of Myeloid-derived Suppressor Cells In Tumor-bearing Mice And Its Correlation With TGF-β₁ Level

Objective:To investigate the changes and distribution of myeloid-derived suppressor cells(MDSCs) in tumor tissues of tumor-bearing mice, analyze the correlation between MDSCs in peripheral blood and serum level of TGF-β1, and explore its significance and mechanisms in hepatocarcinoma immune escape.Methods:Orthotopic transplantation tumor model of hepatocarcinoma in mice was established. On days 7,14, and 21 after tumor inoculation, the proportion of MDSCs in tumor tissues and peripheral blood were analyzed by flow cytometry; the location of MDSCs in tumor tissues was detected by immunohistochemistry; the level of serum TGF-β1 was tested by enzyme-linked immunosorbent assay; the correlation between MDSCs in peripheral blood and serum level of TGF-β1 was analyzed by Pearson correlation, and these were compared with healthy mice as controls.Results:1. The proportion of MDSCs in liver of healthy mice was (1.62±0.82)%, on days 7,14, and 21 after tumor inoculation, its proportion was (9.12±2.26)%,(14.40±2.87)%,(26.27±8.65)% respectively. The proportion of peripheral blood MDSCs in healthy mice was (3.54±2.15)%, on days 7,14, and 21 after tumor inoculation, its proportion was (9.45±2.64)%,(16.40±5.55)%,(25.28±11.32)% respectively. The proportion of MDSCs in tumor tissues and peripheral blood were significantly higher than those in control group(P<0.05), and accompany with tumor progression, the proportion of MDSCs increased gradually.2. Immunohistochemistry staining with anti-Gr-1 antibody was used to examine the location of MDSCs in tumor tissues, it showed that there were a few MDSCs in liver of healthy mice, MDSCs were found mainly in the invasive front of tumor tissues in tumor-bearing mice, and the proportion of MDSCs increased gradually accompany with tumor progression.3. The serum level of TGF-(β1 in healthy mice was (4.89±1.45) ng/ml, on days 7,14, and 21 after tumor inoculation, its proportion was (14.07±6.01) ng/ml,(23.98±3.27) ng/ml,(9.17±1.22) ng/ml respectively. The serum level of TGF-β1 in tumor-bearing mice was statistically higher than those in control group(P<0.05).4. The correlation between MDSCs in peripheral blood and serum level of TGF-β1 was analyzed by Pearson correlation, it indicated that there was a significantly positive correlation between MDSCs in peripheral blood and serum level of TGF-β1(r=0.564, P＜0.05). Conclusion:Accompany with tumor progression, the proportion of MDSCs in tumor tissues and peripheral blood increased gradually, suggesting a close relationship between MDSCs in tumor-bearing mice and tumor progression. MDSCs were accumulated in tumor tissues especially in the invasive front, the proportion of peripheral blood MDSCs was positively correlated with serum level of TGF-β1, these suggested that MDSCs can exert their immunosuppressive function through interaction with tumor cells and secretion of immunosuppressive TGF-β1, induce tumor immune escape, promote tumor cells growth,invasion and metastasis.