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: Professor Carsten Watzl, Technical University of Dortmund, Germany
- Second opponent: Professor Susanne Gabrielsson, Karolinska Institutet, Sweden
- Third member and chair of the evaluation committee: Associate Professor June Helen Myklebust, University of Oslo
Chair of the Defence
Professor Erik Dissen, University of Oslo
Principal Supervisor
Professor Marit Inngjerdingen, University of Oslo
Summary
During the past decades immunotherapy has revolutionized the field of cancer treatment. Several cell-based therapies are currently in the clinic as a second-line treatment, and NK-cell based therapies are showing promise in several clinical trials. However, cellular therapies for solid tumors are facing challenges such as poor tumor infiltration and suppressive signals from the tumor microenvironment, hampering the efficacy of the treatment.
We hypothesized that extracellular vesicles (EVs) derived from NK cells could share similar anti-tumor effects, and could act as an alternative therapy form that would be less sensitive to the hostile tumor microenvironment.
The aims of the thesis were to characterize different subpopulations of NK-EVs, their anti-tumor capacities towards solid cancers and how they interact with the cancer cells.
Comparison of cytokine activated primary NK cells or NK cell lines showed that the cellular source was more important for cytotoxicity than the activation protocol used to generate EVs. Also, NK-EVs showed variable sensitivity towards different solid tumor spheroids, indicating a level of specificity towards certain surface structures.
By comparing the microRNA profile across different NK-EV subpopulations we found an enrichment of microRNAs associated with apoptotic pathways in the cytotoxic subpopulation. This indicate that miRNA might be involved in the killing mechanisms of NK-EVs.
Overall, our studies highlight the potential of NK-EVs as future immunotherapy with high anti-tumor capacities and specificity.
Additional information
Contact the research support staff.