The liver is the second most frequent site of metastases and hepatectomy is still the only corresponding curative treatment, especially for patients with multiple liver metastases. Unfortunately, liver surgery is complex and associated with risks of morbidity and mortality. In some cases, to be able to remove extensive parts of tissue bearing tumors, two-stage hepatectomy takes advantage of the unique regenerative capacity of the liver. The aim is to surgically trigger the growth of the remaining part of the liver that can support liver function after resection. This rapid growth of new functional tissue has huge potential implications in regenerative medicine. Although this process has been studied in many models, how liver regeneration occurs in humans remains elusive. Our first aim is to integrate multiple state-of-art analyses to study the (i) molecular, (ii) cellular and (iii) soluble events during liver regeneration in patients to better understand this process and pre! dict liver failure after two-stage hepatectomy. Although not commonly thought of as an immunological organ, the liver contains large numbers of immune cells and recent studies in mouse models using partial hepatectomy models revealed the key role of immune cells during liver regeneration, especially Natural Killer (NK) cells, innate lymphocytes highly enriched in the human liver. By studying the immune system inside the liver, we have recently reported on the existence of liver-resident NK cells with specific phenotype and functions. However, how the human immune system evolves inside the liver during regeneration and whether these liver-resident cells play a specific role in this process are unclear. Our second aim is to define a role for the intrahepatic immune system in regulation of liver regeneration in a human clinical study. Addressing these aims in a fully human setting with advanced technologies, we anticipate generating novel basic biological understanding applicable in the clinic.