Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Group Leader Roser Vento-Tormo, Wellcome Sanger Institute, UK
- Second opponent: Professor Andreas Lundqvist, Karolinska Institutet, Sweden
- Third member and chair of the evaluation committee: Professor Shuo-Wang Qiao, University of Oslo
Chair of the Defence
Associate Professor Victor Greiff, University of Oslo
Principal Supervisor
Professor Karl-Johan Malmberg, University of Oslo
Summary
Natural Killer (NK) cells play an important role in eliminating infected and transformed cells, including tumor cells. In recent years there has been an increased interest in using NK cells for cellular therapies against cancer. An increased understanding of the biology of NK cells and how different subsets and states of NK cells operate and respond to their environment can aid in efforts to improve NK cell-based therapies. The thesis provides a single-cell characterization of NK cells and established a transcriptional reference map of human NK cells. The reference map allowed for characterization of the perturbed states within tumor-infiltrating NK cells as these could be compared to the reference data. We identified six new states of NK cells, found across blood, tissues and tumors. Of particular interest, we identified a stressed state and a cytotoxic state, both of which were enriched across tumors. Analysis of overall survival of cancer patients showed these to be clinically relevant across different cancer types. The ratio of cytotoxic to stressed NK cells was positively associated with survival, highlighting the role NK cells can play as effectors against tumors. This might inform the design of NK cells for use in therapy. The thesis also provides an analysis of NK cells stimulated with IL-15 to capture the transcriptional profiles associated with NK subsets after stimulation. This data facilitated analysis of NK cells derived from induced pluripotent stem cells. These cells, known as iNK cells, is an important source of cells for the development of cellular therapies. The analysis provided in the thesis showed the iNK cells to exhibit an immature phenotype, but that they also display a cytotoxic profile. Genetically edited iNK cells were analyzed and compared to normal NK cells. This identified gaps in the transcriptional and regulatory repertoire of these cells which provides opportunities for further engineering to design better therapies in the future.
Additional information
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