title: Association of immunoescape mechanisms with Epstein-Barr virus infection in nasopharyngeal carcinoma.
abstract: We have investigated the association of immunoescape mechanisms in nasopharyngeal carcinoma (NPC) lesions with Epstein-Barr virus (EBV) infection and clinical course of the disease. Tumor biopsy specimens obtained from 36 Japanese NPC patients were examined for antigen processing machinery component and HLA class I antigen expression, CD8(+) T cell infiltration, and Fas, Fas ligand (FasL) and IL-10 expression using immunohistochemical staining. The results were correlated with the histopathological characteristics of the lesions, the clinical course of the disease and EBV infection. LMP2, TAP1, tapasin and HLA class I antigens were downregulated in more than 65% of the lesions tested, while FasL, Fas and IL-10 were expressed in at least 60% of the lesions. Statistical analysis showed that (i) HLA class I antigen expression was significantly correlated with LMP2 and tapasin expression (r = 0.39 and 0.45, respectively); (ii) CD8(+) T cell infiltration into tumor lesions was significantly correlated with HLA class I antigen, LMP2 and Fas expression (r = 0.34, 0.49 and 0.44, respectively); (iii) LMP2 and FasL expression was significantly correlated with IL-10 expression (r = 0.49 and 0.52, respectively); (iv) IL-10 expression was significantly associated with EBERs and EBV oncoprotein LMP1 expression (p = 0.00078 and 0.015, respectively) and (v) FasL overexpression was significantly associated with reduced patients' survival (p = 0.033). Multivariate analysis identified FasL overexpression as an independent unfavorable prognostic marker. These results suggest that NPC cells may utilize multiple immunoescape mechanisms, including dysfunction of HLA class I antigens and Fas/FasL apoptosis pathways. Furthermore, FasL expression appears to be associated with IL-10 upregulation in EBV positive NPC cells.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Asahikawa, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogino
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Moriai
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Ishida
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ishii
authors.forename: Akihiro
authors.initials: A
authors.lastname: Katayama
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miyokawa
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Harabuchi
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D053222:Fas Ligand Protein / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000821:virology*; D012333:RNA, Messenger / Q000235:genetics; D019014:fas Receptor / Q000276:immunology
chemical_list: D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D019014:fas Receptor; D016753:Interleukin-10