Th22/IL-22 mediates the progression of HBV-related hepatocellular carcinoma via STAT3.

T helper cell 22 are abundant in Hepatitis B Virus-related hepatocellular carcinoma tissue, and the main cytokine interleukin 22 produced by Th22 cells is closely related to the initiation and development of HCC. Understanding the role of Th22/IL-22 in the progression of HBV-related HCC will facilitate new therapeutic development. Th22 cells were isolated from peripheral blood of healthy donors and co-cultured with HBV positive HepG2.2.15 cells. IL-22 secretion and HepG2.2.15 cell proliferation and apoptosis were monitored. Expressions of p-STAT3, Cyclin D1, Bcl-2, and cleaved caspase 3 were detected by Western blot analysis. Th22 cells significantly promoted the proliferation and inhibited the apoptosis of HepG2.2.15 cells; up-regulated expression of p-STAT3, Cyclin D1 and Bcl-2, and down-regulated cleaved caspase 3 in HepG2.2.15 cells. These effects were significantly attenuated when IL-22 and STAT3 was knockdown in Th22 and HepG2.2.15 cells, respectively. Our data suggests that HBV induces host Th22 cells to overexpress IL-22, which in turn triggers over-activation of STAT3 and its downstream signaling proteins to promote HCC progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-021-00517-9.