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Association of immunoescape mechanisms with Epstein‐Barr virus infection in nasopharyngeal carcinoma
Author(s) -
Ogino Takeshi,
Moriai Shigetaka,
Ishida Yoshiya,
Ishii Hideyuki,
Katayama Akihiro,
Miyokawa Naoyuki,
Harabuchi Yasuaki,
Ferrone Soldano
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22334
Subject(s) - fas ligand , nasopharyngeal carcinoma , antigen , human leukocyte antigen , cd8 , epstein–barr virus , immunohistochemistry , tumor infiltrating lymphocytes , biology , antigen processing , virus , immunology , hla dr , pathology , medicine , apoptosis , mhc class i , biochemistry , programmed cell death , radiation therapy
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. © 2007 Wiley‐Liss, Inc.