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 Noel F. de Miranda, Leiden University Medical Center, The Netherlands
- Second opponent: Researcher Xavier Tekpli, Oslo University Hospital,
- Third member and chair of the evaluation committee: Professor Kristin Bjørnland, University of Oslo
Chair of the Defence
Associate Professor Johannes Kurt Schultz, University of Oslo
Principal Supervisor
Professor Kjersti Flatmark, University of Oslo, Group Leader, Department of Tumor Biology, Institute for Cancer Research
Summary
Colorectal cancer is one of most prevalent cancers in the world, and prognosis is dependent on the time of diagnosis. Patients with metastasis have poor prognosis, and for the majority there is no curative treatment available. This group is primarily offered palliative care with chemotherapy and radiation therapy. While recent years have seen a remarkable development in immunotherapy, results from clinical trials for patients with metastatic colorectal cancer have been disappointing. However, infiltration of T cells, a type of immune cell that can recognize and kill tumor cells, has been shown to be a positive predictor of overall survival in colorectal cancer patients.
The aim of this thesis was to use computational approaches to study metastatic colorectal cancer. Using T cell receptor sequencing, we showed that chemotherapy was associated with higher T cell infiltration in a brief time interval prior to liver resection, compared to patients who had not received chemotherapy. T cell infiltration was similar to baseline in patients where there was a longer time interval between therapy and resection. Interestingly, all patients who received chemotherapy also had more clonal T cell repertoires.
In other parts of this work, we compared sequencing data of microRNA and RNA between liver, lung and peritoneal metastasis. We found a robust signature of microRNA expression alterations in metastasis, and also found a subtype of peritoneal metastasis with a distinct immune profile.
These results underline the importance of the timing of drug administration in combination therapies, which is currently being investigated in the METMMOX randomized control trial. The results have also improved our understanding of metastasis, and are excellent starting points for future studies.
Additional information
Contact the research support staff.