Our paper "Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy" was included in the February 2022 EACR's regular summary of the 10 most interesting and impactful recent papers in cancer research.
In this paper, we 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. We discovered that DTCs lay preferentially dormant in the liver, and spatially distinct liver sub-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.
Read more here.
Read the paper in Nature.