Effect Of Sorafenib On Aberrant Expression Of P-STAT3 In Peripheral Blood CD4~+T, CC8~+T And Treg Cells Of Patients With Hepatocellular Carcinoma

Aim:To study the effect of sorafenib on aberrant expression of p-STAT3 in peripheral blood CD4~+T, CD8~+T and Treg cells of patients with hepatocellular carcinoma. Learn more about the relative importance and function of the IL-6/STAT3 signaling pathway in malignancy. Provide a theoretical basis for the clinical targeted therapy of sorafenib.Methods:Anticoagulated and non-anticoagulated peripheral blood was collected from patients with HCC who is taking sorafenib treatment and healthy controls. p-STAT3 levels in peripheral blood CD4~+T, CD8~+T and Treg cells were detected by flow cytometry. Serums were extracted, the production of IFN-y, IL-4, IL-6, IL-10, TGF-?, Granzyme B and perforin in serums were measured by ELISA. Spearman's correlation analysis was used to determine the correlation between the ratio of IFN-y/IL-4 and levels of IFN-y, IL-4, IL-6, and p-STAT3 in CD4~+T cells in patient samples. Spearman's correlation analysis was used to determine the correlation between the levels of IL-6, Granzyme B, perforin, and p-STAT3 in CD8~+ T cells. Spearman's correlation analysis was used to determine the correlation between the levels of IL-6, IL-10, TGF-?, and p-STAT3 in Treg cells.Results:The expression of p-STAT3 in CD4~+T cells from patients with HCC after taking sorafenib treatment were all lower than before (p<0.001). The expression of p-STAT3 in CD8~+ T cells from patients with HCC after taking sorafenib treatment were all lower than before (p<0.001). The expression of p-STAT3 in Treg cells from patients with HCC after taking sorafenib treatment were all lower than before (p<0.001). The expression of IFN-y, Granzyme B, perforin levels in serum of HCC patients after taking sorafenib treatment were higher than before (p<0.001). whereas, IL-4, IL-6, IL-10 and TGF-p levels in serum after taking sorafenib treatment were all lower than before (p<0.001). The ratio of IFN-y/IL-4 and the levels of IFN-y correlated negatively with p-STAT3 in peripheral CD4~+cells in patient samples, however, the levels of IL-4 correlated positively with p-STAT3 in peripheral CD4~+ cells in patient samples. The levels of Granzyme B, perforin correlated negatively with p-STAT3 in peripheral CD8~+ T cells in patient samples. The levels of IL-10, TGF-P correlated positively with p-STAT3 in peripheral Treg cells in patient samples. The levels of IL-6 correlated positively with p-STAT3 in peripheral CD4~+, CD8~+ and Treg cells in patient samples.Conclusions:Sorafenib is closely related to the expression of the p-STAT3 in peripheral blood CD4~+T, CD8~+T and Treg cells from patients with HCC. The mechanism may be related block the IL-6/STAT3 signaling pathway and improve the immune system. The expression of p-STAT3 and the levels of IL-6 was up-regulated in peripheral CD4~+, CD8~+ and Treg cells of HCC patients contributed to HCC pathogenesis.