Guanylate-binding proteins(GBPs) are interferonstimulated factors involved in the defense against cellular pathogens and inflammation. These proteins, particularly GBP-1, the most prominent member of the family, have ...Guanylate-binding proteins(GBPs) are interferonstimulated factors involved in the defense against cellular pathogens and inflammation. These proteins, particularly GBP-1, the most prominent member of the family, have been established as reliable markers of interferon-γ-activated cells in various diseases, including colorectal carcinoma(CRC) and inflammatory bowel diseases(IBDs). In CRC, GBP-1 expression is associated with a Th1-dominated angiostatic micromilieu and is correlated with a better outcome. Inhibition of tumor growth by GBP-1 is the result of its strong antiangiogenic activity as well as its direct anti-tumorigenic effect on tumor cells. In IBD, GBP-1 mediates the anti-proliferative effects of interferon-γ on intestinal epithelial cells. In addition, it plays a protective role on the mucosa by preventing cell apoptosis, by inhibiting angiogenesis and by regulating the T-cell receptor signaling. These functions rely to a large extent on the ability of GBP-1 to interact with and remodel the actin cytoskeleton.展开更多
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 car...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.展开更多
基金Supported by German Research Foundation,No.DFG-KFO257(sub-project 4)No.SFB796(sub-project B9)+1 种基金No.DFG-BR5196,and No.FOR2438(sub-project 2)Interdisciplinary Center for Clinical Research(IZKF)of the Clinical Center Erlangen
文摘Guanylate-binding proteins(GBPs) are interferonstimulated factors involved in the defense against cellular pathogens and inflammation. These proteins, particularly GBP-1, the most prominent member of the family, have been established as reliable markers of interferon-γ-activated cells in various diseases, including colorectal carcinoma(CRC) and inflammatory bowel diseases(IBDs). In CRC, GBP-1 expression is associated with a Th1-dominated angiostatic micromilieu and is correlated with a better outcome. Inhibition of tumor growth by GBP-1 is the result of its strong antiangiogenic activity as well as its direct anti-tumorigenic effect on tumor cells. In IBD, GBP-1 mediates the anti-proliferative effects of interferon-γ on intestinal epithelial cells. In addition, it plays a protective role on the mucosa by preventing cell apoptosis, by inhibiting angiogenesis and by regulating the T-cell receptor signaling. These functions rely to a large extent on the ability of GBP-1 to interact with and remodel the actin cytoskeleton.
基金German Research Foundation.Grant Numbers:FOR2438,280163318DFGSFB/TRR241,375876048+2 种基金DFGSTU238/10-1,437201724DFGTRR305,429280966DFG-NOTICE,493624887 Interdisciplinary Center for Clinical Research Programm zur Förderung von Corona-Forschungsprojekten W.Lutz Stiftung Forschungsstiftung Medizin am Universitätsklinikum Erlangen German Federal Ministry of Education and Research.Grant Numbers:01KT1801,031L0262C Chinese scholarship program。
文摘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.
