{'fraction_non_alphanumeric': 0.040021344717182494, 'fraction_numerical': 0.0288153681963714, 'mean_word_length': 5.009615384615385, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Decreased EBNA-1-specific CD8+ T cells in patients with Epstein–Barr virus-associated nasopharyngeal carcinoma

The Epstein–Barr virus (EBV) nuclear antigen-1 (EBNA-1) is potentially a universal target for immune recognition of EBV-infected normal or malignant cells. EBNA-1-specific CD8+ T-cell responses have been assessed against a few epitopes presented on a limited number of HLA class I alleles. We now assess CD8+ T-cell responses to a complete panel of EBNA-1 peptides in an HLA-characterized population. We detected EBNA-1-specific CD8+ T cells in 10 of 14 healthy donors by analysis of peripheral blood mononuclear cells and EBV-specific T-cell lines. The frequent detection of CD8+ T-cell responses was confirmed by mapping EBNA-1 epitopes and demonstrating HLA class I presentation to CD8+ T cells in 6 of 6 donors, including 2 new EBNA-1 epitopes presented by HLA A0206 and A6802. Importantly, EBNA-1-specific CD8+ T cells were significantly less frequent in EBV-specific T-cell lines from patients with EBV-associated nasopharyngeal carcinoma (3 out of 22, P = 0.0003), whereas the frequency of LMP2-specific responses (14 out of 22) was not significantly different from healthy donors (11 out of 14). EBNA-1-specific CD8+ T-cell responses were rescued in approximately half of nasopharyngeal carcinoma patients by peptide and cytokine stimulation of peripheral blood mononuclear cells, suggesting these EBNA-1-specific CD8+ T cells were functionally defective in their response to EBV-infected cells. These results indicate that humans normally mount a significant EBNA-1-specific CD8+ T-cell response to EBV infection, but the immune response to this tumor antigen has been significantly altered in nasopharyngeal carcinoma patients. Overcoming this defect in EBV-specific immunity may prevent or enhance treatment of EBV-associated nasopharyngeal carcinoma.