Effect of Sorafenib on Myeloid-derived suppressor cells in HCC

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related deaths worldwide. Sorafenib, a multikinase inhibitor, is the first-line systemic therapy approved for advanced HCC, but its impact on the tumor microenvironment, particularly on myeloid-derived suppressor cells (MDSCs), is not fully understood.MDSCs are a heterogeneous population of immune cells that play a crucial role in promoting tumor growth and immune evasion by suppressing T cell function and facilitating an immunosuppressive microenvironment. This study investigates the effects of sorafenib on the function and phenotype of MDSCs in HCC. Overall design: In this study, we first established a hepatocellular carcinoma (HCC) model in C57BL/6 mice using the murine HCC cell line Hepa1-6. Tumor cells were subcutaneously injected into the flanks of C57BL/6 mice to induce tumor formation. Once tumors reached a measurable size, mice were sacrificed, and peripheral blood was collected for further analysis.Myeloid-derived suppressor cells (MDSCs) were isolated from the peripheral blood using flow cytometry. The cells were characterized and sorted based on the surface markers CD45+7aad-CD11b+Gr-1+. The purity of the sorted MDSCs was verified through additional flow cytometric analysis.Isolated MDSCs were then subjected to in vitro treatment with sorafenib for 72 hours. The treatment concentration of sorafenib was optimized based on preliminary dose-response experiments to ensure effective modulation of MDSC function without inducing significant cytotoxicity.After the 72-hour treatment period, MDSCs were harvested and used for subsequent experiments