Assessing T-cell responses to Epstein-Barr virus in individuals at risk for nasopharyngeal carcinoma

Elevated Epstein-Barr virus (EBV) antibody levels are associated with risk of nasopharyngeal carcinoma (NPC) and risk scores based on these antibodies can predict NPC risk with high accuracy. The immune mechanisms underlying this association remain unclear. We evaluated whether individuals with elevated EBV-NPC antibody risk scores had a reduced T-cell response to EBV proteins within a NPC multiplex family study in Taiwan. In total, 79 cancer-free individuals from families with a history of NPC had blood tested for (i) EBV antibodies using a multiplex serology assay and (ii) T-cell responses to 7 EBV proteins (EBNA1, LMP1, LMP2, BZLF1, BRLF1, BARF1, gp350) using interferon-γ ELISPOT. Excluding individuals with low phytohemagglutinin proliferative responses, no statistically significant association was observed between lower EBV T-cell responses and higher EBV antibody-based NPC risk scores (P = 0.21). However, our findings did trend in the a-priori hypothesized direction, with lower EBV T-cell responses noted among those with higher EBV antibody-based NPC risk scores. Compared to individuals who responded to at least 3 EBV-specific T-cell peptide pools by ELISPOT, those who responded to 1–2 peptide pools had a 10% increased risk of having an EBV-NPC risk score above the median value (OR = 1.1; 95% CI = 0.3, 4.5) and those who responded to none had a 3-fold increased risk (OR = 3.0; 95% CI = 0.6, 17). Our study is the first to evaluate whether high EBV antibody responses observed among individuals at risk of NPC are associated with reduced T-cell responses to EBV. Our findings suggest such an association but require replication in larger studies.