Expression of Immune-Related Molecules in Primary EBV Positive Chinese Nasopharyngeal Carcinoma: Associated with Latent Membrane Protein 1 (LMP1) Expression

Jiang Li, Xiao-shi Zhang, Dan Xie, Hai-xia Deng, Yan-fang Gao, Qiu-yan Chen, Wen-lin Huang, Maria G. Masucci and Yi-Xin Zeng

volume 6 | issue 12

December 2007
Pages: 1997 - 2004

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To understand the role of Epstein-Barr virus (EBV) and viral products in associated with immunophenotype and clinical outcome of primary nasopharyngeal carcinoma (NPC), the expression levels of chemokines IFN-γ-induced protein 10 (IP-10, CXCL10), stromal-derived factor-1 (SDF-1, CXCL12) and its receptor CXCR4 was investigated in 56 primary NPC biopsy specimens from Chinese NPC patients in parallels with LMP1 antigen and EBER1 by immunohistochemisty (IHC) and in situ hybridization (ISH). Moreover, the expression levels of HLA class I (β-microglobulin) and II antigen (HLA-DR), and co-stimulatory molecule CD54 were also evaluated in 31 out of these 56 patients using immunohistochemisty (IHC). Our results showed that (a) the elevated expression levels of IP10, SDF-1, CXCR4, β-microglobulin, HLA-DR, and CD54 in NPC lesions was 66%, 36%, 30%, 42%, 55% and 69%, respectively. (b) High expression of SDF-1 was observed in advanced NPC (N stage, P<0.05). (c) LMP1 expression correlated with up-regulation of CXCR4 and translocation of CXCR4 to the nucleus of the tumor cells. This role of LMP1 in regulating the expression of CXCR4 was confirmed in the EBV positive NPC cell line C666 by inhibition of LMP1 expression with small interfering RNA (siRNA). Our findings provide new insights on the immune status of the malignant cells which may affect the outcome of immunotherapy in NPC.