Exogenous and endogenous virus interactions in head and neck cancer immunity (105.34)

We report that two common tumor viruses etiologically associated with head and neck cancer, Epstein-Barr virus (EBV) with undifferentiated nasopharyngeal carcinoma, and human papillomavirus (HPV) with oropharyngeal squamous cell carcinoma, transactivate an endogenous retrovirus (HERV-K18), which encodes a superantigen that activates TCRBV13 T cells. EBV LMP-2 transactivated the HERV-K18 superantigen in nasopharyngeal epithelial cells, and EBV-associated nasopharyngeal carcinomas expressed the superantigen. HPV type-16 E6 and E7 proteins also transactivated the HERV-K18 superantigen in oropharyngeal epithelial cells, and superantigen expression was significantly increased in HPV16-associated carcinomas. Serum cytokine levels in head and neck carcinoma patients indicated that there were distinct inflammatory profiles associated with exogenous and endogenous viruses. HPV-associated patients had increased levels of serum IL-8, while HPV-negative patients had higher serum IL-6 and G-CSF levels. Interestingly, HERV-K18 superantigen levels correlated independently with serum levels of the Th2 cytokine IL-13. Among HPV+ tumors, gene expression array analyses indicated that B cell specific genes were significantly upregulated in the superantigen high group. Our results suggest that endogenous superantigen expression in HPV+ tumors was associated with a Th2 immune response, demonstrating that chronic and endogenous viruses comprising the virome affect both host and tumor immunity.