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Molecular Characterization of Antigen-processing Function in Nasopharyngeal Carcinoma (NPC): Evidence for Efficient Presentation of Epstein-Barr Virus Cytotoxic T-Cell Epitopes by NPC Cells¹

EBV Unit, Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia [R. K., S. R. B., D. J. M., L. C.]; Laboratoire de Biologie des Tumeurs Humaines, URA 1156 CNRS, Insitut Gustave Roussy, 94805 Villejuif, Cedex, France [P. B.]; Department of Pathology, University of Hong Kong, 5 Sassoon Road, Hong Kong, People's Republic of China [J. M. N.]; and Laboratoire d'Immunologie et d'Histocompatibilite, Hospital Saint-Louis, 75475 Paris, Cedex 10, France [C. R.]

Potentiation of the EBV-specific CTL response by immunization with CTL epitopes has been proposed as a logical approach for immunetargeting nasopharyngeal carcinoma (NPC) cells in vivo. This approach will undoubtedly be influenced by the ability of these malignant cells to endogenously process and present target epitopes on their cell surface for immune recognition by CTLs. Analysis of NPC cells in fresh tumor biopsies and long-term, established NPC tumors in nude mice revealed normal expression of the MHC-encoded putative peptide transporters TAP1 and TAP2, as well as the proteasome components LMP2 and LMP7, which have been shown previously to be essential components of the class I processing pathway. Moreover, these tumor cells also showed high levels of HLA class I alleles on the cell surface, suggesting that peptides are available for binding to nascent MHC molecules in the endoplasmic reticulum. Using a recombinant vaccinia virus to transiently express the EBV nuclear antigens, we studied the antigen-processing efficiency of NPC cells. Our findings demonstrate that, in contrast to cells from another EBV-associated malignancy, Burkitt's lymphoma, NPC cells display normal antigen-processing function and are efficiently recognized by HLA class I-restricted, virus-specific CTLs. These studies also provide a rationale for focusing on strategies designed to activate CTLs specific for EBV antigens that are expressed in NPC cells in vivo.

¹ This work was supported by grants from the Queensland Cancer Fund (Brisbane, Queensland, Australia). R. K. was supported by an R. D. Wright Fellowship from the National Health and Medical Research Council (Canberra, Australia). P. B. was supported by the Association pour la Recherche contre le Cancer Grant 2037.

² To whom requests for reprints should be addressed, at EBV Unit, Queensland Institute of Medical Research, Bancroft Centre, 300 Herston Road, Brisbane, Queensland 4029, Australia. Phone: 61-7-3362-0346; Fax: 61-7-3362-0106.

Received 7/14/97. Accepted 11/13/97.

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