The combined HPV16-E2/E6/E7 T cell response in oropharyngeal cancer predicts superior survival.

Santegoets, Saskia J; Stolk, Anouk; Welters, Marij J P; van der Burg, Sjoerd H · Cell Rep Med · 2023

prospective_cohort · Level II

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Abstract

Tumor-infiltrating HPV16-E2-specific CD8<sup>+</sup> T cells have been detected in HPV16-induced oropharyngeal squamous cell carcinoma (OPSCC). Whether intratumoral CD4<sup>+</sup> T cells target HPV16 E2 and if HPV16-E2-specific immunity contributes to better clinical outcome is unknown. In a prospective HPV16<sup>+</sup> OPSCC cohort, we regularly detect HPV16-E2-specific CD4<sup>+</sup> and CD8<sup>+</sup> 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.

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