Characterisation of tumour heterogeneity in tissue slice cultures of head and neck tumours

• Applicant: Dr. Rasmus Sönnichsen
• Subject Area: Otolaryngology, Phoniatrics and Audiology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 549149350

New immunotherapeutics are becoming increasingly important in the treatment of head and neck tumours. However, the response to therapy varies and a reliable predictive marker for identifying sensitive cohorts has not yet been identified. For this reason, ex vivo test systems are becoming increasingly important for individualised therapy decisions in head and neck oncology. In addition, they can help to better understand the mechanisms of action and the influence on the tumour microenvironment. Tissue slice cultures enable the examination of patient-specific tumour tissue with the corresponding tumour microenvironment over several days and therefore have the potential to close this gap. However, the extent to which the original heterogeneity of tumour cells and immune cells is reflected in tissue thin-section cultures and how many tissue sections are required for a representative sample has not yet been sufficiently investigated. In this project, the first step is therefore to adapt the tissue slice culture system for head and neck tumours and to characterise it in particular with regard to tumour heterogeneity. To this end, the stability of tumour and immune cells in the cultures will be investigated using (multiplex) immunostaining and any changes in the spatial cell distribution within the tissue sections will be analysed over the culture period. A particular focus here is on various immune cells such as T lymphocytes, B lymphocytes and macrophages, as these are particularly relevant in the context of new immunotherapeutics. The histological analyses are supplemented by cytokine analyses from the medium supernatants of the tissue slice cultures, which provide additional information on the functional status of the cells contained in the tissue sections. In a second step, tissue slice cultures of head and neck tumours are stimulated with interferon gamma. The aim is to investigate the effects of this pro-inflammatory cytokine on the tumour microenvironment and the possibility of influencing it. This project will enable tissue slice cultures of head and neck tumours to be used for the analysis of (immune) cell-specific changes under pharmacological pressure while taking the important aspect of tumour heterogeneity into account. This will enable subsequent projects to specifically analyse the mechanisms of action of current and future therapeutics in head and neck tumours.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Andreas Weigert