Frequency of Epstein-Barr virus-specific cytotoxic T lymphocytes in the blood of Southern Chinese blood donors and nasopharyngeal carcinoma patients.
Undifferentiated nasopharyngeal carcinoma is very common among Southern Chinese. While most patients have the disease detected and treated early, those who are diagnosed with advanced stages face a poor prognosis. Nasopharyngeal carcinoma is associated with latent Epstein-Barr virus (EBV); it was suggested previously that a cytotoxic T-lymphocyte (CTL)-based therapy targeting EBV proteins may offer a possible new form of treatment for this disease. The most likely target of this treatment is latent membrane protein 2 (LMP2). To define further the preexisting level of anti-EBV immunity in Chinese subjects, the frequency of peripheral blood mononuclear cells (PBMCs) responding to peptide epitopes was determined using an ELISPOT assay in 50 healthy control blood donors and in 26 patients newly diagnosed with nasopharyngeal carcinoma. A total of 7 LMP2, 2 LMP1, 1 EBNA3A, and 1 EBNA3B epitopes were used in a HLA-restricted manner. As reported previously for healthy virus carriers in western countries, it was found that in both groups the strongest responses were to epitopes in the EBNA proteins with weaker responses to the LMP epitopes. It was found that LMP2 epitopes were recognized in a greater percentage of both groups than previously reported, due most likely to the greater sensitivity of the ELISPOT method. However, patients with nasopharyngeal carcinoma demonstrated a weaker response than that displayed by healthy control subjects to several epitopes. The results demonstrate that LMP2 epitopes are recognized widely in an HLA-restricted manner in patients with nasopharyngeal carcinoma and that immunotherapy to boost preexisting immunity to these epitopes may offer a viable method to treat such patients or to protect against recurrence.
Whitney
Bruce M
BM
Hong Kong Cancer Institute, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, N.T. Hong Kong SAR, People's Republic of China. brucemwhitney@cuhk.edu.hk
Chan
Anthony T C
AT
Rickinson
Alan B
AB
Lee
Steven P
SP
Lin
C K
CK
Johnson
Philip J
PJ
D000595:Amino Acid Sequence; D001782:Blood Donors; D002277:Carcinoma / Q000276:immunology* / Q000821:virology; D002681:China; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology; D006680:HLA Antigens / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000821:virology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; D006680:HLA Antigens; D010455:Peptides; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D007371:Interferon-gamma