Christoph Schifflers

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Analysis of the immunomodulatory effects of irradiation on human papillomavirus-driven vs carcinogen-driven head and neck squamous cell carcinoma

Several strains of human papillomavirus (HPV) significantly increase the risk to develop malignancies, including head and neck squamous cell carcinoma (HNSCC). The prognosis and treatment response of HPV-driven HNSCC is considerably better than of HPV-negative HNSCC. Importantly, HPV-driven HNSCC exhibit increased radiosensitivity when compared to their HPV-negative counterparts. While cancer cell intrinsic factors partially explain the observed difference, the immune response also seems to play a major role in the differential radiation response.

This project aimed to determine if HPV-related immunogenicity of HNSCC cancer cells after irradiation favors an efficient anti-cancer immune response and immune-memory formation, improving HNSCC response to radiation treatment. We addressed the difference in immunogenicity of HPV-driven and HPV-negative HNSCC before and after radiation, and assessed how immunogenic cell death and dendritic cell maturation is changed, and focused on differential PD-L1 expression, which was shown to be affected by HPV status. In addition, a novel HPV-driven base of tongue tumor model was developed in immunocompetent MHC-humanized mice.