INS and colonic neoplasm: Apart from the essential roles in metabolism and cell stemness, insulin and EGF are involved in the up-regulation of PD-L1 expression in colon cancer stem cell (CSCs), suggesting that the inhibition of insulin and EGF/EGFR pathways can be considered for cancer immunotherapy, either alone or in combination with PD-1/PD-L1 antibody-based cancer immunotherapy to eliminate CSCs [71].