title: Elevated blood levels of soluble tumor necrosis factor receptors in nasopharyngeal carcinoma: correlation with humoral immune response to lytic replication of Epstein-Barr virus.
abstract: Nasopharyngeal carcinoma (NPC) is tightly associated with Epstein-Barr virus (EBV) infection and a heavy infiltration of lymphoid cells in the tumor tissue. Although various lines of evidence have shown that the immune systems of NPC patients have the potential to attack the tumor cells, it is not yet understood how this potential is blocked. In this study we determined the circulatory soluble tumor necrosis factor receptors (sTNFRI and sTNFRII), which are proven to be inhibitory to the anti-tumor effects of tumor necrosis factor-alpha (TNF-alpha), in NPC patients. The serum concentration of both sTNFRI and sTNFRII was determined with an ELISA method, and shown to be significantly higher in 28 NPC patients than in matched healthy controls. This elevation was found to be positively correlated with the serum titers of IgA against EBV early antigens and viral capsid antigens in NPC patients, suggesting that the increased serum concentration of sTNFRI and sTNFRII is possibly due to the EBV infection in NPC tumor cells. This is partly supported by FACS analysis of the circulatory T cells. Phenotypical expression of activation markers such as CD25, CD38, CD69 and CD71 in blood T cells was not significantly different between the NPC and control individuals, indicating the elevation of the sTNFRs is indeed derived from the local immune response in the tumor area. Based on these results, it seems that the increased sTNFRs may act as an inhibitor to decrease the host immune response towards tumor cells in NPC patients.
authors.affiliation: Department of Microbiology, National University of Singapore, Singapore 119260, Republic of Singapore.
authors.forename: P
authors.initials: P
authors.lastname: Feng
authors.forename: S H
authors.initials: SH
authors.lastname: Chan
authors.forename: E E
authors.initials: EE
authors.lastname: Ooi
authors.forename: M Y
authors.initials: MY
authors.lastname: Soo
authors.forename: K S
authors.initials: KS
authors.lastname: Loh
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: E C
authors.initials: EC
authors.lastname: Ren
authors.forename: H
authors.initials: H
authors.lastname: Hu
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D015703:Antigens, CD / Q000097:blood*; D000956:Antigens, Viral / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood*; D036022:Capsid Proteins; D002277:Carcinoma / Q000097:blood* / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000097:blood* / Q000453:epidemiology / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007157:Immunologic Surveillance; D015994:Incidence; D007371:Interferon-gamma / Q000097:blood; D018655:Lymphocyte Count; D009303:Nasopharyngeal Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D009363:Neoplasm Proteins / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012846:Singapore / Q000453:epidemiology; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D015703:Antigens, CD; D000956:Antigens, Viral; D014408:Biomarkers, Tumor; D036022:Capsid Proteins; C041788:Epstein-Barr viral capsid antigen; C033305:Epstein-Barr virus early antigen; D007070:Immunoglobulin A; D009363:Neoplasm Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma