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

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Abstract

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.

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