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 beta (TGF-beta) has dual functions in tumors-tumor promoter or tumor suppressor. As a tumor promoter, TGF-beta 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-b and CD8(+) CTLs levels and their relationship in human hepatocellular carcinoma (HCC). Immunohistochemical staining was conducted to analyze the prognostic value of TGF-b expression and/ or CD8(+) CTLs levels in 407 HCC patients. The relationship between TGF-b and CD8(+) T-cellwas also evaluated usingHCC cell lines and patients' peripheral blood. Lower TGF-b expression or a higher CD8(+) CTL density was associated with better overall survival and recurrence-free survival, and the patients with low TGF-b expression and more CD8(+) CTLs had the best prognosis. Although there was no correlation between TGF-b 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-beta. Furthermore, the TGF-beta levels was not associated with the proportion of CD8(+) T cells, but negatively related to interferon g secretion by CD8(+) T cells in peripheral blood of HCC patients. Higher TGF-beta also resulted in decreased interferon g secreted by CD8(+) T cells in vitro. In conclusion, our study suggests that TGF-beta 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.