Santegoets et al. demonstrated the presence of intratumoral HPV16 E2-specific CD4+ and CD8+ T cells in a previously described prospective HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC) cohort. T cell reactivity was detected across the entire E2 protein. E2-specific cells were less abundant than E6/E7-specific T cells in OPSCC and cervical cancer and were polyfunctional, although more polyfunctional T cells were E6/E7-reactive. The presence of HPV16-E2-specific T cell reactivity further improved the clinical impact, as HPV16+ OPSCC patients with T cells producing type 1 cytokines to both E2 and E6/E7 displayed superior survival.
Contributed by Shishir Pant
ABSTRACT: Tumor-infiltrating HPV16-E2-specific CD8(+) T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4(+) T cells 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 T cells, albeit at lower frequencies than the co-infiltrating HPV16-E6/E7-specific T cells. These HPV16-reactive T cells produce multiple cytokines when activated, indicating their polyfunctionality. Importantly, their combined intratumoral presence predicts superior survival, emphasizing the value of HPV16-E2-specific T cells in anti-tumor immunity and suggests its use as a target antigen for immunotherapy.