Yupingfeng Granule Improves Th2-Biased Immune State in Microenvironment of Hepatocellular Carcinoma through TSLP-DC-OX40L Pathway

The tumor immunological microenvironment in hepatocellular carcinoma (HCC) is the T-helper (Th) 2 dominant inhibition state. Improving the immunosuppressive tumor microenvironment represents an important strategy for HCC treatment. TSLP-OX40L pathway is a target to improve Th2 immunosuppression. Yupingfeng granule (YPF) is clinically used to effectively improve the immune status of HCC. In this study, YPF increased the percentage of mature dendritic cells (DCs) and decreased levels of TSLP, TSLPR, and OX40L in tumor and adjacent tissues of the orthotopic-HCC mice model. This occurs together with the decreased levels of Th2 cytokines and increased levels of Th1 cytokines and Th1/Th2 ratio. In vitro experiment showed that YPF not only increased the percentage of mature DCs and stimulated IL-12 secretion in DCs but also reduced the positive rate of OX40L expression, decreased the proportion of CD4(+) IL-13(+) T cells, increased levels of Th1 cytokines, and decreased levels of Th2 cytokines from TSLP-treated DCs. In summary, these findings demonstrated that YPF promoted the maturation of DCs, decreased OX40L in TSLP-induced DCs, and improved the immunosuppressive state of Th2 in HCC microenvironment. Our results suggest that the mechanism underlying the improving effect of YPF on the immunosuppression is related to the DC-mediated TSLP-OX40L pathway.