Transient metabolic state lets a single cancer cell evade immunity and seed lung metastases

Researchers identified a transient metabolic and epigenetic state that lets a tiny subset of disseminated tumor cells evade immune clearance and establish secondary tumors in mice. The state features elevated PHGDH enzyme activity, which adds a histone methylation mark suppressing immune-signaling genes, creating an "immune-scarce" sanctuary. Surviving cells remained quiescent, then lost PHGDH expression before proliferating into metastases. Spatial transcriptomic analysis tracked lung metastasis over a month, showing most secondary tumors descended from briefly high-PHGDH cells. Macrophages also helped build a welcoming niche, highlighting a dynamic process with potential intervention windows.