Abstract
We have investigated the association of immunoescape mechanisms in nasopharyngeal carcinoma (NPC) lesions with EpsteinโBarr 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 ILโ10 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 ILโ10 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 ILโ10 expression (r = 0.49 and 0.52, respectively); (iv) ILโ10 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 ILโ10 upregulation in EBV positive NPC cells. ยฉ 2007 WileyโLiss, Inc.