Immune modulatory activity of activated hepatic stellate cells in the tumor microenvironment / 中华肝胆外科杂志

ABSTRACT

Objective To determine immune modulatory activity of activated hepatic stellate cells( HSCs) in hepatocellular carcinoma and immune response in tumor microenvironment. Methods Cell proliferation was measured by BrdU incorporation with a microtiter plate reader at 450 nm. The effect of HSCs on T cell proliferation was measured by MLR. Mouse hepatic cancer cell line H22 were implanted on the backs of BALB/c mice to establish the subcutaneous transplanted tumor model. Then the mice were sacrificed after 20 days for anatomical and size determination. Furthermore, Paraffin-embedded tissue was removed by serial tissue sectioning and immunohistochemically examined for expression of T lymphocyte subsets. T lymphocyte subsets in splenocytes were detected by FCM. Apoptotic mononuclear cells were evaluated by FITC-labeled Tunel assay. Results We determined that HSCsCM promoted hepatocellular carcinoma(HCC) cell line proliferation and HSCs inhibit T cell proliferation by MLR in vitro. We also examined normal immune mice to assess the immunosuppression of HSCs in the development of HCC. In the co-transplantation with HSCs group, T cells and their subtypes decreased obviously in the tumors and the spleen. The results showed that co-transplanted HSCs can induce more PD-L1 expression and more mononuclear cell apoptosis in tumor tissue. Conclusion Our results demonstrated that HSCs promote HCC progression partially because of their immune regulatory activity. Our data supply new information to support an integral role for HSCs in promoting HCC progression and suggest that HSCs may serve as a therapeutic target for HCC.