Many aspects of metastasis, or the spread of cancer to other parts of the body, remain puzzling. We do know that, in many patients with cancer, tumour cells that broke away from the primary tumour enter into a “sleeping” condition after arriving at distant tissues, and persist there for many years or decades until they are “woken up” at some point. However, how these cells are put to sleep and what finally triggers them to awaken and grow unchecked are one of the most fundamental unsolved problems in oncological research.  

The research team led by Ana Luisa Correia sought to contribute a scientific piece of the jigsaw towards solving this puzzle. She developed a tool to follow the dormant tumour cells. One of her insights was that the dormant tumour cells from mice with breast cancer accumulated frequently in the liver, where they are under control of endogenous natural killer cells (NK). Killer cells are known to be part of the innate immune system and to be capable of recognising and killing cancer cells. 

The scientist demonstrated that the size of the killer cell pool in the liver is decisive to the question of whether or not tumour cells remain dormant – if there is a reduction in these defence cells, cancer cells revive again. The number of killer cells is influenced by hepatic stellate cells (HSCs), which upon activation inhibit killer cells. Such stellate cells assist liver regeneration upon injury, but also appear to play a central role in the formation of metastases.  

The Basel scientist and her research team concluded from the newly obtained data that an anti-metastatic therapy should promote the preservation of a large population of natural killer cells, that maintains cancer cells asleep as long as possible. These insights are already being integrated into a first clinical study at the University Hospital Basel.

Hepatic stellate cells suppress NK cellsustained breast cancer dormancy. Ana Luísa Correia, Joao C Guimaraes, Priska Auf der Maur, Duvini De Silva, Marcel P Trefny, Ryoko Okamoto, Sandro Bruno, Alexander Schmidt, Kirsten Mertz, Katrin Volkmann, Luigi Terracciano, Alfred Zippelius, Marcus Vetter, Christian Kurzeder, Walter Paul Weber, Mohamed Bentires-Alj. 
Nature. 2021 Jun;594(7864):566-571. doi: 10.1038/s41586-021-03614-z.