Identification of tumor and stroma antigens for the treatment of HNSCC

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Head and neck squamous cell carcinoma is a frequent cancer and associated with poor prognosis. Therefore, new therapeutic strategies are urgently required for this tumor entity. Cancer immunotherapy has recently emerged as a promising treatment modality in a number of cancers and may also improve clinical outcome in HNSCC patients. In other cancer types spontaneous tumor-specific T cell responses are correlated with increased T cell infiltration in tumors, improved prognosis and response to treatment and may thus represent a promising resource for cancer immunotherapy. For HNSCC we found that spontaneous tumor specific T cell responses as well as T cell infiltration are also associated with an improved prognosis. However, in order to clinically exploit the endogeneous repertoire of tumor reactive T cells for diagnosis and treatment, determination of the target antigens of such responses is mandatory. We have recently developed a novel technology that for the first time allows an unbiased and comprehensive identification of T cell target antigens in tumor tissues, which is not restricted to tumor cell-associated antigens but can also be used to identify tumor stroma-associated antigens. Within this project we will determine major target antigens of spontaneous T cell responses in the tumor tissue of HNSCC patients and assess in particular the role of tumor-associated fibroblasts as targets of protective T cell immunity since they are not subjected to immune editing, are homogeneously expressed throughout on the whole tumor tissue and since the tumor stroma is indispensable for tumor maintenance and progression. By T cell receptor (TCR) sequencing we will determine whether T cells specific for selected tumor cell- and fibroblast-associated antigens accumulate within the tumor tissue. We will characterize expression of selected major T cell target antigens in a larger cohort of HNSCC tumors and finally assess their prognostic relevance for overall survival. On this basis, we will select a panel of HNSCC-associated antigens with potential relevance for T cell based cancer immunotherapy.