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.

Objective Accumulating reports have suggested that hepatic stellate cells (HSCs) exhibit immunosuppressive ability and may be responsible for the occurrence and development of hepatocellular carcinoma (HCC).The mechanisms through which HSCs affect T-cell-induced adaptive immune responses and the relationship with the regulatory T cells (Treg cells) were studied.Methods We isolated HSCs from wildtype mice to demonstrate the influence of HSCs on T-cell proliferation and explored their effect on Treg cells through mixed leukocyte reactions (MLRs) in vitro.Results We found that activated HSCs could induce T-cell hyporesponsiveness in adaptive immune response by inhibiting the proliferation of T cells andincreasing the quantity of Treg cells.Conclusion Activated HSCs may lead to hypoergia of T cells in adaptive immune reaction and up-regulate the expression of Treg cells,thus facilitating immunotolarance.

Objective To study the correlation between lactate/albumin ratio level and incidence of multiple organ dysfunction syndrome (MODS) as well as mortality in patients with severe sepsis or septic shock.Methods In January 2012-September 2013, 54 patients who were admitted to the intensive care unit(ICU) of a hospital developed severe sepsis and septic shock on the first day of admission, clinical data of patients were analyzed.Results On the first and second days of admission, 30(55.56%)and 26(53.06%)patients developed MODS;lactate/albumin ratio between MODS group and non-MODS group on the first and second days of admission were both significantly different (both P<0.05).Multivariate logistic regression analysis showed that lactate/albumin ratio, oxygenation index (PaO2/FiO2), as well as acute physiology and chronic health evaluation (APACHE Ⅱ) were independent risk factors for predicting MODS in patients with severe sepsis.Lactate/albumin ratios between MODS group and non-MODS group, death group and non-death group were both significantly different (both P<0.05);lactate/albumin ratio was correlated with APACHE Ⅱand PaO2/FiO2, the higher the APACHE Ⅱ score and the lower the PaO2/FiO2, the higher of lactate/albumin ratio.The area under the receiver operating curve (ROC curve) analysis showed that incidence and mortality of MODS on the first day of admission predicted by lactate /albumin ratio were 0.85 and 0.84 respectively;sensitivity, specificity, positive predictive value, and negative predictive value of occurrence of MODS predicted by lactate /albumin ratio>1.735 were 80.00%, 79.17%, 82.67%, and 75.92% respectively, sensitivity, specificity, positive predictive value, and negative predictive value of mortality were 100.00%, 51.02%, 17.23%, and 100.00% respectively.Conclusion Lactate/albumin ratio level is closely correlated with incidence and mortality of MODS in patients with severe sepsis or septic shock.