Irradiated whole-cell vaccine suppresses hepatocellular carcinoma growth in mice via Th9 cells.

Abstract

Liver cancer is one of the most common malignant tumors with no available satisfactory treatment. The aim of the present study was to investigate the anti-tumor effect of an irradiated hepatocellular carcinoma (HCC) whole-cell vaccine and its underlying mechanisms. Hepa1-6 and H22 HCC cell lines were irradiated in preparation for whole-cell vaccine production. Subsequently, two HCC tumor-bearing mouse models were created by injecting these Hepa1-6 and H22 cells into the abdominal skin of C57BL/6 and ICR mice, respectively. The mice were immunized with the corresponding whole-cell vaccine the next day, and then once a week until the end of the experimental period. Tumor growth, blood T helper (Th)9 cells and plasma interleukin (IL)-9 levels were monitored during the immunization period. Th9 cells were also induced by in vitro co-culture of the whole-cell vaccine with lymphocytes from the spleen and lymph nodes of the corresponding mice. Alterations of gene expression in transcription factor (TF) were determined by reverse transcription-quantitative PCR, and Th9 cells were detected using flow cytometry. The whole-cell vaccine effectively suppressed HCC tumor growth, as indicated by slower tumor growth and a smaller tumor size in the immunized group compared with the control. The percentage of blood Th9 cells and the concentration of plasma IL-9 were significantly increased in the immunized group. The whole-cell vaccine also induced Th9 cell differentiation and upregulated the expression of TFs PU.1, interferon regulatory factor 4 and basic leucine zipper transcriptional factor ATF-like. These results suggest that the irradiated HCC whole-cell vaccine inhibited tumor growth by increasing Th9 cell numbers in HCC mice