Tumor microenvironment-dependent epigenetic imprinting in the vasculature predicts colon cancer outcome

Dear Editor,Tumor microenvironment(TME)-dependent stromal cell plasticity governs tumor development and therapy response.Tumor endothelial cells(TECs)are a major cellular component in this context[1].In colorectal carcinoma(CRC),the stromal cell-dependent impact of the TME is illustrated by an improved survival depending on an interferon(IFN)-γ-dominated Th1-like TME associated with high T-cell density[2]and suppressed angiogenesis[3,4].Cellular transcriptional memory is reported in cell lines after repeated exposure to IFN-γin vitro[5],suggesting that a Th1-like TME may also exert stable imprinting effects in vivo.Here,we investigated whether TME-dependent transcriptional imprinting in TECs from CRC patients can be exploited to retrieve clinically relevant signatures predicting outcomes.