Molecular and immune landscape of colorectal liver metastases

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 a significantly lower complication rate (19% vs 31%), shorter hospital stay (53 vs 96 hours) at a similar cost. The 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 exposed to neoadjuvant chemotherapy (NACT). Almost all analysed cases were microsatellite stable, which is associated with poor response to immunotherapy. Quantification of T-cell densities by immunohistochemistry in primary CRC and matched CLM showed low concordance. T-helper cell 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 (