Background: Intratumoral T-cell abundance is an established predictor of improved survival in and neck squamous cell carcinoma (HNSCC). Antigen-specific immune response is a hallmark of cancer immunotherapy. Potential antigens in HNSCC include tumor-associated antigens (TAAs) and viral proteins, including high-risk human papillomavirus (HPV) proteins. Studies combining multiple antigens for cellular therapy renewed interest in TAAs.

Methods: Intratumoral T-cell abundance in a large retrospective cohort of HNSCC patients was analyzed using an adapted immune score. RNA expression of TAAs and genes associated with antigen presentation were assessed by 3" RNA Sequencing of treatment naïve HPV-positive and HPV-negative HNSCC tumor samples and matched healthy mucosa. Endogenous T cell and humoral responses against viral proteins and TAAs were determined by FluoroSpot and protein-bound bead assays. Expression of components of the HLA class I antigen presentation pathway was analyzed in a large cohort of HPV-positive and HPV-negative HNSCC patients and correlated to intratumoral immune cell abundance.

Results/Conclusion: Increased Intramural T-cell infiltration was associated with improved survival and positive HPV status. Endogenous antigen specific T-cell responses against viral antigens and TAAs were frequently detectable and nuanced differences in relation to p16 and HPV DNA status were identified. Humoral responses directed at the same antigens were partially overlapping with T-cell responses. New results will be presented in the context of previously published literature regarding antigen-specific immune response and antigen expression in HNSCC.

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