Expression of HLA class I, beta(2)-microglobulin, TAP1 and IL-10 in Epstein-Barr virus-associated nasal NK/T-cell lymphoma: Implications for tumor immune escape mechanism.

Several mechanisms of immune escape might be in operation in Epstein-Barr virus (EBV)-associated nasal NK/T-cell lymphoma. We have previously shown the downregulation of the immunogenic EBV nuclear antigens by alternative promoter usage and the preferential selection of the deletion genotype of latent membrane protein 1 in nasal lymphoma. To understand further the strategies used for immune escape by this tumor, we examined by immunohistochemistry HLA class I expression in 15 cases using frozen sections, along with beta(2)-microglobulin and transporter associated with antigen processing 1 (TAP1) expression in 39 cases using paraffin sections. All nasal NK/T-cell lymphomas showed positive staining for HLA class I, beta(2)-microglobulin and TAP1 on most tumor cells, except for two cases (5%) in which most of the tumor cells lacked beta(2)-microglobulin staining. We next immunostained for interleukin-10 on frozen sections in 13 cases, all of which showed strong expression by most tumor cells. Transcription of human interleukin-10 but not EBV BCRF1 (viral interleukin-10) was identified by reverse transcriptase-polymerase chain reaction in these nasal NK/T-cell lymphomas. Overall, our data suggest that global downregulation of HLA class I or TAP1 rarely accounts for the ability of nasal NK/T-cell lymphoma to evade immunosurveillance and that other immune escape mechanisms may be operating in nasal NK/T-cell lymphoma, such as production of interleukin-10 to suppress the local immune response.