Elevated serum levels of transforming growth factor β1 in Epstein‐Barr virus‐associated nasopharyngeal carcinoma patients

Abstract

Nasopharyngeal carcinomas (NPCs) of non‐keratinizing type are strongly associated with Epstein‐Barr virus (EBV). EBV and its gene products induce the synthesis and/or release of transforming growth factor β1 (TGF‐β1) from human cells and platelets. TGF‐β1 is an immunosuppressive cytokine, and many tumors are known to secrete it, to counter the host immune response. To determine the potential role of this cytokine in the pathogenesis of NPC, 53 serum samples from patients with EBV‐associated NPC and 20 from healthy donors were analyzed for total and active TGF‐β content using ELISA. Serum samples for TGF‐β content were also analyzed from NPC patients at different clinical stages of the tumors. Significantly higher (p < 0.01) levels of active and total TGF‐β were found in the sera of NPC patients than in control sera. The ratio of active:total TGF‐β was also significantly (p < 0.01) increased in the NPC sera. Levels of this cytokine were also significantly higher (p < 0.05) in the sera of patients with advanced stages of tumor compared to patients with earlier stages. Furthermore, higher levels were seen in patients with relapsing than with remitting tumors; even higher levels were observed in NPC patients who died of the tumor. Our data suggest a role of this cytokine in the pathogenesis of NPC; therefore, it may prove to be a valuable biomarker molecule for the diagnosis and prognosis of NPC. Int. J. Cancer (Pred. Oncol.) 84:396–399, 1999. © 1999 Wiley‐Liss, Inc.

A strategy for treatment of Epstein–Barr virus-positive Hodgkin's disease by targeting interleukin 12 to the tumor environment using tumor antigen-specific T cells

“…10,40 IL12-transduced CTL may also be of interest for other infections, such as HIV, in which the progressive loss of Th1 cytokine production is thought to play a major role in the development of the immunodeficiency syndrome. 41 …”

Elevated Serum Transforming Growth Factor β1 Levels in Epstein-Barr Virus-Associated Diseases and Their Correlation with Virus-Specific Immunoglobulin A (IgA) and IgM

“…Serum samples were obtained from healthy EBV-seropositive and -seronegative volunteers and from patients suffering from EBV-induced IM, CEI, BL, and NPC. The criteria for the diagnosis of these patients have been detailed in our recent publications (24,25). The CEI patients in this study had prolonged severe relapsing courses of IM with high titers of antivirus capsid antigen and EBV early antigen antibodies in serum and little or no antibody to the EBV nuclear antigens.…”

“…Recently, we reported that the levels of TGF-␤ are significantly increased in the sera of patients with EBV-associated, undifferentiated, and poorly differentiated nasopharyngeal carcinoma (NPC) (25). EBV is a ubiquitously occurring human gamma herpesvirus and has been etiologically associated with several disease conditions, including different malignancies and lymphoproliferative disorders (reviewed in reference 20).…”

“…The CEI patients in this study had prolonged severe relapsing courses of IM with high titers of antivirus capsid antigen and EBV early antigen antibodies in serum and little or no antibody to the EBV nuclear antigens. Since TGF-␤ is secreted in a latent form (which becomes activated by a yet poorly understood mechanism before interacting with the TGF-␤ receptors on cells), we measured the concentrations of total TGF-␤ as well as of its active form in serum by using a commercial enzyme-linked immunosorbent assay (ELISA) kit (Promega, Madison, Wis.) as we described earlier (25). The mean values for different groups were compared by using Student's t test as described earlier (24).…”

“…As shown in Table 3, higher TGF-␤ levels correlated with increased positivity of sera for anti-gp350 antibodies of the IgA isotype. We further analyzed the relationship between TGF-␤ levels and different anti-gp350 titers by multiple regression analysis (25). As shown in Table 4, irrespective of the disease condition, TGF-␤ levels correlated positively (P Յ 0.01) only with gp350-specific IgA titers, suggesting that higher TGF-␤ levels in these patients may be driving (probably along with human IL-10 and/or its viral homologue) the enhanced production of anti-EBV IgA.…”