Abstract
Tumor-infiltrating HPV16-E2-specific CD8+ Tcells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4+ Tcells target HPV16 E2 and if HPV16-E2-specific immunity contributes to better clinical outcome is unknown. In a prospective HPV16+ OPSCC cohort, we regularly detect HPV16-E2-specific CD4+ and CD8+ intratumoral Tcells, albeit at lower frequencies than the co-infiltrating HPV16-E6/E7-specific Tcells. These HPV16-reactive Tcells produce multiple cytokines when activated, indicating their polyfunctionality. Importantly, their combined intratumoral presence predicts superior survival, emphasizing the value of HPV16-E2-specific Tcells in anti-tumor immunity and suggests its use as a target antigen for immunotherapy.
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