LGR5 and cancer: The expression of PD-L1 on cancer cells can be directly upregulated by MACC1 itself [127], or through secondary factors such as HGF/c-MET [166], via activated STAT1/3 [167], PI3K/Akt [155], or Wnt/β-catenin signaling [160], from metabolic alterations [168] or by promoting cellular stemness via Oct4/NANOG/LGR5 [169].