Science Sub-journal: Reveals THE anti-tumor immune response of GCN2 inhibits tumor microenvironment

The protein GCN2 (general control nonderepressible 2) is an environmental lying protein that controls transcription and translation based on nutritional availabilityAlthough GCN2 is a potential therapeutic target in immuno-oncology, its role in shaping the tumor immune response is unclearIn a new study, researchers from Canada, the United States, Brazil and Italy used mass spectrometry, transcriptometography, and transcription factor binding analysis to determine the functional effects of GCN2 on myelin-suppressing cell phenotypes and immune responses in melanomaThe findings were recently published in the journal Science Immunology under the title "GCN2 drives macrophage and MDSC function and immunosuppression in the tumor microenvironment"images from Science Immunology, 2019, doi: 10.1126/sciimmunol.aax8189they found that the absence of GCN2 in myeloid inhibition cells promotes phenotypes of tumor-related macrophages and myelin-like inhibition cells, thereby promoting an anti-tumor immune responseflight time mass spectrometry cell technology (time-of-flight mass cytometry, CyTOF) and single-cell RNA sequencing indicate that this is due to changes in the tumor microenvironment: an increase in the pro-inflammatory activation of macrophages and myelin-like inhibition cells, and interferon-sepsis expression in CD8-T cells in tumorsinstitutionally, GCN2 has changed the function of myelin-inhibited cells by facilitating the translation of transcription factor CREB-2/ATF4, where CREB-2/ATF4 is necessary for macrophages and myelin inhibition cells in mice and humans, and can reduce tumor growth by targeting Atf4 with small interference RNAfinally, analysis of patients with skin melanoma showed that the transcriptional characteristics of GCN2 dependence were negatively correlated with macrophage polarization, T-cell immersion, and overall survivalreferences:Marie Jo Halaby et alGCN2 macro drivesphage and MDSC function and abysuppression in tumor the car microenvironmentScience Immunology, 2019, doi: 10.1126/sciimmunol.aax8189.