PDCD1 and cancer: For instance, optimal cancer therapy with inhibition of the PD-1/PD-L1 axis should include: (1) modulation at the tumor site due to the localized expression pattern of PD-L1 in the TME, (2) targeting of elevated immune inhibitory cytokines (IL10, TGF-β), tumor metabolites and regulatory cells, and (3) rescue of the tolerated tumor immunity (177).