Characterization and functional analysis of cancer-antigen specific tumour immune infiltrates from patients with head and neck squamous cell carcinoma

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I) To characterize the phenotype and functional capability of CD8+ and CD4+ T-cells in different compartments of head and neck squamous cell carcinoma. To this end, immune cells from tissue samples of primary tumours, draining lymph nodes and the peripheral blood will be isolated. The primary focus will lie in the analysis of tissue resident memory cells, which are likely enriched for cancer antigen specificity. II) To understand the link between the T-cell recognition of mutated and shared target antigens, the density and composition of immune infiltrates and the presence of cancer-antigen specific immunity. The repertoire of potential target antigens in tumour biopsies will be characterized by whole tumour sequencing of exome DNA and total RNA. We will use bioinformatics pipelines established in Southampton to predict mutated neoantigens and to quantify the expression of shared cancer antigens (viral antigens, cancer-testis antigens). Tumour infiltrating immune cells from the respective patients will be expanded and tested for reactivity to selected target antigens. III) To determine the effect of neoadjuvant treatment with anti-PD-1 antibodies on tumour infiltrating immune cells. Experiments will be carried out in analogy to aim 2 in diagnostic pre-treatment biopsies and samples after neoadjuvant PD-1 antibody treatment from the time of surgical resection.