Importantly, the hypoxic TME also drives upregulation of biomarkers such as PD-L1 on circulating tumor cells (CTCs), which represents a mechanism of adaptive immune resistance; PD-L1-positive CTCs interact with PD-1 on T cells to dampen immune surveillance and are now being explored as predictors of ICI response (42, 43). This evidence concerns the gene PDCD1 and neoplasm.