Nika Vučković

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Effect of chemoradiotherapy on the immunopeptidome of HPV16-positive cervical and head and neck cancer cell lines

Cervical cancer (CxCa) and a subset of head and neck squamous cell carcinoma (HNSCC) are predominantly associated with a persistent Human Papillomavirus (HPV), majority of which are caused by HPV16. HPV oncoproteins E6 and E7, crucial for the transformation of infected cells by disruption of the cell cycle and prevention of apoptosis, are always present in HPV-driven cancer cells. Peptides derived from E6 and E7 constitute the cancer cells´ immunopeptidome and are a promising basis for a therapeutic HPV vaccine, the overarching goal of the Riemer group. To that end, a targeted liquid chromatography mass spectrometry (LC/MS) method that allows detection of low-abundance epitopes, such as HPV-derived viral ones, was established by in-group and already led to identification of several HLA-presented HPV16-derived epitopes. For both advanced CxCa and HNSCC patients first-line standard-of-care is chemoradiotherapy; yet, patients with HPV-positive diagnosis have a more favourable prognosis than patients with HPV-independent cancer, and reports show that chemoradiotherapy has an immunomodulatory effect.  By in vitro mimicking the treatment regimens applied in the clinic, we aim to assess chemoradiotherapy effects on the HLA-presentation of HPV16 epitopes. Insight gained into the effect of chemoradiation on the immunopeptidome of treated CxCa and HNSCC is one of the factors that allow progress towards the design and implementation strategy of an effective therapeutic HPV vaccine.