Since elevated PD-L1 expression in tumour cells or TME cells is a result of various molecular events including hypoxia (168), and since activation of hypoxia inducible factor (HIF) is a key molecular hallmark in the metastatic progression of Pheo/PGL (169, 170), it has been hypothesized that activation of the hypoxic response might promote cancer-specific immune-tolerance through expression of PD ligands and thus facilitate malignant progression in Pheo/PGL (171). This evidence concerns the gene CD274 and neoplasm.