Digital Public Defence: Vegar Johansen Dagenborg

MD Vegar Johansen Dagenborg at Institute of Clinical Medicine will be defending the thesis “Molecular and immune landscape of colorectal liver metastases” for the degree of PhD (Philosophiae Doctor).

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Photo: Beate Willumsen.

The public defence will be held as a video conference over Zoom.

The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.

Click here to participate in the public defence

Download Zoom here

Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.

Order a digital copy of the thesis here

Digital Trial Lecture – time and place

See Digital Trial Lecture.

Adjudication committee

  • First opponent: Professor Sabine Tejpar, Leuven University Hospital
  • Second opponent: Associate Professor II Kim Erland Mortensen, UiT Norges arktiske universitet
  • Third member and chair of the evaluation committee: Associate Professor Viktor Berge, University of Oslo

Chair of the Defence

Professor Egil Johnson, Faculty of Medicine, University of Oslo

Principal Supervisor

Professor II Kjersti Flatmark, Faculty of Medicine, University of Oslo 

Summary

Colorectal cancer is a common cancer in both genders, and 50% develop metastases which is the dominating cause of death from CRC, most frequently located in the liver (CLM). Only 20% of patients with CLM are eligible for surgical resection. For the first time in a randomised study, the OSLO-COMET trial compared short-term outcome between open and laparoscopic resection in 280 patients. Laparoscopic resection had significantly lower complication rate (19% vs 31%) and shorter hospital stay (53 vs 96 hours) at a similar cost, and postoperative 90-day mortality was low (0.04%). The long-term outcome after CLM resection may be associated with molecular and immunological features. Based on analysis of samples from the OSLO-COMET biobank the most frequent mutations were located in the TP53, APC, KRAS, PIK3CA, SMAD4, and NRAS genes, and the cohort was enriched for consensus molecular subtype 2. Importantly, the identified transcriptomic changes suggested that immune activation had taken place in tumours exposure to neoadjuvant chemotherapy (NACT). Almost all analysed cases were microsatellite stable, which is associated with poor response to immunotherapy.  Quantification of T-cells densities by immunohistochemistry in primary CRC and matched CLM showed low concordance. T-helper dominated with regulatory T-cells comprising up to 44%, suggesting immune suppression. T-cells accumulated in the invasive tumour margin, particularly in CLM. A short-interval (<9.5 weeks) between NACT exposure and CLM resection was strongly associated with high T-cell density, including cytotoxic T-cells.

In conclusion, the short-term results of the OSLO-COMET trial support the use of laparoscopy for CLM resection. Analyses of molecular and immunological features suggested the presence of immune suppression in CLM, and that NACT induces a transient immune activation that could be exploited in future studies in combination with immune therapy.

Additional information

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Published June 11, 2021 10:15 AM - Last modified June 16, 2021 11:50 AM