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: Associate Professor Emily Mace, Columbia University Irving Medical Center
- Second opponent: Professor Fredrik Bergh Thorén, University of Gothenburg
- Third member and chair of the evaluation committee: Professor Michael Rory Daws, University of Oslo
Chair of the Defence
Associate Professor Andreas Lossius, University of Oslo
Principal Supervisor
Professor Karl-Johan Malmberg, University of Oslo
Summary
This thesis explores how natural killer (NK) cells can be better used to treat cancer. NK cells are important members of the innate immune system that can recognize and kill cancer cells without prior training, making them promising candidates for immunotherapy. However, a major challenge is that NK cells often fail to reach and enter solid tumors, limiting their effectiveness.
The research conducted in this thesis focuses on how NK cells move within the body. Their movement is controlled by proteins called chemokine receptors, which guide them toward specific signals (chemokines). The study mapped which receptors are present on different NK cell subtypes and found that activating two different receptors at the same time can significantly improve their ability to migrate.
By analyzing 9471 tumor samples from publicly available datasets, it was discovered that most solid tumors do not produce the right combination of signals to attract NK cells. This helps explain why NK cells are often absent in these tumors.
To further investigate NK cell behavior, a method was developed to temporarily “turn off” specific genes in NK cells using small interfering RNA (siRNA). To develop the method, genes with known function were targeted with siRNA and tested for their loss of gene and protein expression, and function. This approach allows researchers to study gene function in NK cells in conditions closer to their natural state.
Using this method, we identified that a protein called GPR56 acts as a “brake” on NK cell movement. When this protein is reduced or blocked, NK cells move more effectively while increasing their effector function, suggesting it could be targeted to improve cancer treatments.
Overall, the thesis provides new insights into how NK cells migrate and identifies strategies to enhance their ability to reach tumors, which could lead to more effective immunotherapies for solid cancers.
Additional information
Contact the research support staff.