Development of a 3D organoid model of oropharyngeal cancer for the purpose of studying anti-tumour immunity.

This PhD project is primarily focussed on the development of 3D organoid cultures that incorporate some of the key features of tonsillar tissue, such as tissue architecture and cell populations. Organoid cultures have emerged as an attractive system to study epithelial regeneration and in vitro disease modelling, and for preclinical assessment of efficacy for immune-oncology therapeutics.

This project involves sorting of single-cells from primary tissue and epithelial cell lines originating from OPC samples using multicolour flow cytometry, and development of cell culture conditions which will be evaluated in terms of effects on cell viability, growth and tissue structure. It includes analysis of cell types which have the capacity to regenerate, i.e. cancer stem cells, as well as live-cell imaging, immunohistochemistry and proteomic characterization of the self-organizing 3D structures. The organoid cultures will ultimately be used in co-cultures with immune cells isolated from HPV+ and HPV- OPC samples to study suppressive mechanisms and the ability of DC subpopulations to induce efficient anti-tumour CD4+ and CD8+ T responses, and to test novel immunotherapeutic antibodies developed in-house.

Main supervisor of this project is Prof. Malin Lindstedt, Department of Immunotechnology, and co-supervisors are Professor Lennart Greiff from Department of Otorhinolaryngology, Doctor Peter Ellmark from Alligator Bioscience AB and Doctor Christina Sakellariou from the Department of Immunotechnology.