A little help from friends.

Top Line: How do normal cells in the tumor microenvironment (TME) enable tumor development or progression?

The Study: Here are a pair of interesting studies describing how normal cells enable tumor development and progression. Neurofibromatosis, type 1 (NF1) is associated with development of low-grade optic glioma (OPG). This study used a mouse model of NF1-mutated OPG to demonstrate that tumorigenesis is dependent on light-induced neuronal activity. That’s right, when neurons with germline NF1 mutation fire in response to light, they shed increased amounts of neuroligin 3 (NLGN3), which promotes tumorigenesis in other cells. Deprivation of light and blocking NLGN3 negated this effect. Another study used a mouse model of metastatic breast cancer that produces metastatic cells capable of both dormancy at metastatic sites and active metastatic proliferation. They focused on the liver where a mix of both active metastases and scattered dormant cells or cell clusters were found. They found that the relative amount of natural killer (NK) cells and the availability of interferon-gamma in the TME largely determined whether metastatic cells became dormant or proliferate. Interestingly, abundant NK cells in the TME induced a quiescent state rather than direct cell kill. In contrast, hepatic stellate cells (aHSC), which become activated in response to liver injury, depleted NK cells and produced a fibrotic stromal response in the TME that enabled quiescent cancer cells to proliferate into active metastases.

TBL: Non-malignant cells in the TME play key enabling roles in tumor development and metastasis. | Pan, Nature 2021 and Correia, Nature 2021