Figure 3.

Metabolite signaling in the tumor microenvironment Metabolite signaling in cancer-associated cells within the microenvironment. Lactate directly binds to MAVS to suppress RLR signaling and weakens cancer immunosurveillance. Kynurenine metabolism is activated in tumor-associating immune cells. Kynurenine binds to either transcription factor AHR or the cell-surface receptor GPR35 to mediate inflammatory signaling. In Th1 cells, glutamine-derived α-KG increases the expression of Tbet, through an unknown mechanism, and promotes Th1 cell differentiation. Bile acid triggers the release of CXCL16, which further acts on endothelial cells and NK cells to enhance antitumor immunosurveillance. AHR, aryl hydrocarbon receptor; GPR35, G protein–coupled receptor 35; Tbet, T-box transcription factor.