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.

Author Info: (1) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. (2) Department of Medical Oncology, Oncode

Author Info: (1) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. (2) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. (3) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. (4) Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. Electronic address: shvdburg@lumc.nl.