The EACR’s Top 10 Cancer Research Publications is a regular summary of the most interesting and impactful recent papers in cancer research. It is curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors.
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Correia, A.L., Guimaraes, J.C., Auf der Maur, P. et al. Nature 594, 566–571 (2021).
Summary of findings
Tumor cells that spread beyond the primary tumor can enter a dormant state upon arrival at the distant site, only to awaken years (or even decades) later to form deadly metastases. What drives these cells in and out of dormancy is yet to be fully understood. In this Nature paper, Correia et al. developed a tool to follow dormant disseminated tumor cells (DTCs), and surveyed the anatomical distribution of dormant reservoirs in spontaneous metastasis models of breast cancer. They discovered that DTCs lay preferentially dormant in the liver, and spatially distinct liver ts thsub-microenvironments allow coexistence of dormant DTCs and rare growing metastases even within the same tissue. It is the size of the endogenous pool of natural killer (NK) cells within these sub-microenvironmenat controls breast cancer progression. When abundant, NK cells sustain dormancy through interferon-γ signaling, preventing hepatic metastases and prolonging survival. If there is a liver injury, such as liver fibrosis mediated by the accumulation of activated hepatic stellate cells, NK cell proliferation is inhibited and metastases emerge. These findings show that NK cells put cancer cells to sleep, and suggest that therapies aimed at normalizing the NK cell pool might succeed in preventing liver metastases.
“Dormancy in breast cancer is a critical problem and in this study it is shown that NK cells play a critical role in this process.”
EACR Board
Future impacts of the findings
These results yielded direct druggable targets with already approved agents that can be repurposed and readily translated into the clinical setting. For this, the authors are already setting up two clinical trials at the University Hospital of Basel. The first will trace the levels of NK cells in breast cancer patients at high risk of developing metastases, and examine whether those levels correlate with the outcome of these patients. And the second will be an intervention trial to evaluate the potential of adjuvant NK cell immunotherapy to prevent metastatic disease in breast cancer patients.
