Transforming Growth Factor β is a Poor Prognostic Factor and Inhibits the Favorable Prognostic Value of CD8+ CTL in Human Hepatocellular Carcinoma.

It is widely understood that transforming growth factor β (TGF-β) has dual functions in tumors-tumor promoter or tumor suppressor. As a tumor promoter, TGF-β drives tumor initiation and progression partially by suppressing the antitumor responses of CD8 cytotoxic T lymphocytes (CTLs) in the tumor microenvironment. Here, we investigated the prognostic value of measuring TGF-β and CD8 CTLs levels and their relationship in human hepatocellular carcinoma (HCC). Immunohistochemical staining was conducted to analyze the prognostic value of TGF-β expression and/or CD8 CTLs levels in 407 HCC patients. The relationship between TGF-β and CD8 T-cell was also evaluated using HCC cell lines and patients' peripheral blood. Lower TGF-β expression or a higher CD8 CTL density was associated with better overall survival and recurrence-free survival, and the patients with low TGF-β expression and more CD8 CTLs had the best prognosis. Although there was no correlation between TGF-β expression and the density of CD8 CTLs, the survival of patients with more CD8 CTL cells was only significantly improved when the tumor expressed low levels of TGF-β. Furthermore, the TGF-β levels was not associated with the proportion of CD8 T cells, but negatively related to interferon γ secretion by CD8 T cells in peripheral blood of HCC patients. Higher TGF-β also resulted in decreased interferon γ secreted by CD8 T cells in vitro. In conclusion, our study suggests that TGF-β is a poor prognostic factor for patients and negatively affect the prognostic value of CD8 CTLs through suppressing antitumor activity of CD8 T-cell in HCC.