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TNF-a is produced by activated macrophages, T and B lymphocytes, natural killer cells, astrocytes, endothelial cells, smooth muscle cells, some tumor cells, and epithelial cells
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Amino acid metabolic alterations, particularly upregulation of indoleamine 2,3-dioxygenase 1 (IDO1) and arginase-1 (ARG1), result in kynurenine accumulation and L-arginine depletion, synergistically suppressing T cell function while reinforcing MDSC activation [131]