Serum and Tissue Level of TLR9 in EBV-Associated Oropharyngeal Cancer

SIMPLE SUMMARY: The Epstein–Barr virus (EBV) is associated with the development and progression of various epithelial malignancies including cancer in the head and neck region. Toll-like receptors (TLRs) are molecules distinguishing self and non-self antigens. They are required for congenital immune response to infections with viruses such as EBV because, during viral infection, the congenital immunity is the first line of human defense preventing the replication of the virus. Moreover, TLR response may influence the transformation to malignancy. The aim of our study was to assess TLR9 level in patients with diagnosed oropharyngeal cancer with or without EBV infection. We wanted to know whether infection with EBV influences TLR9 level and maybe changes the immune response which may lead to malignant transformation. The results obtained in our research may improve understanding of the role viral infections play in head and neck cancers and influence future diagnosis, prevention and treatment strategies in these malignancies. ABSTRACT: The Epstein–Barr virus (EBV) is associated with the development of various epithelial malignancies including cancer in the head and neck region. Several studies have shown that Toll-like receptors (TLRs) are required for an innate immune response to infection with human DNA viruses, e.g., EBV. During viral infections, TLR response may influence the transformation to malignancy. The aim of the study was to assess TLR9 serum and tissue level in EBV(+) and EBV(−) oropharyngeal cancer patients. The study involved 78 patients: 42 EBV(+) and 36 EBV(−). EBV DNA was detected in fresh frozen tumor tissue. TLR9 level was measured in homogenate of tumor tissue and in serum. Moreover, in serum samples IL-10, VEGF, TGFβ, TNFα and antibodies against EBV were detected using ELISA test. TLR9 level was significantly lower in EBV(+) patients, both in tissue and serum, while EBVCA, EBNA and VEGF level was statistically higher in EBV(+) patients. An increase in EBVCA and EBNA antibodies titer was correlated with a TLR9 level decrease. TLR9 level was higher in poorly-differentiated tumors (G3), in tumor of larger dimensions (T3-T4) and with lymph nodes involvement (N3-N4) but without statistical significance. High levels of anti-EA antibodies in the majority of EBV(+) patients may point to the reactivation of EBV infection.