title: Transforming Growth Factor β is a Poor Prognostic Factor and Inhibits the Favorable Prognostic Value of CD8+ CTL in Human Hepatocellular Carcinoma.
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.
authors.affiliation: Departments of *Endoscopy ‡Hematological Oncology §Intensive Care Unit ∥Head and Neck Surgery ¶Hepatobiliary Oncology, Sun Yat-sen University Cancer Center †State Key Laboratory of Oncology in South China, Guangzhou, China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Liao
authors.forename: Feng
authors.initials: F
authors.lastname: Han
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Li
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Chen
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Lao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000401:mortality; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000401:mortality; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016212:Transforming Growth Factor beta; D007371:Interferon-gamma