Emerging evidence demonstrates that lactate accumulation within hypoxic tumor regions induces histone lactylation and reprograms macrophages toward M2-like phenotypes, adenosine generated via CD73 up-regulation suppresses CD8+ T-cells, and bile acids activate CAFs via GPBAR1 to foster neutrophil recruitment and immunosuppressive stroma in CCA (32, 33). This evidence concerns the gene GPBAR1 and cholangiocarcinoma.