Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

Figure 1 Regulatory mechanism of programmed death-1/programmed death ligand 1 signaling in cancer. The interaction between programmed death-1 and programmed death ligand 1 (PD-L1) leads to the inhibition of T cell functional activation. PD-L1 expression in cancer cells is regulated by aberrant oncogenic pathways. PD-1: Programmed death-1; PD-L1: Programmed death ligand 1; TCR: T cell receptor; ITSM: Immunoreceptor tyrosine-based switch motif; ITIM: Immunoreceptor tyrosine-based inhibitory motif; IRF: Interferon regulatory factor.

Figure 2 The complexity of hepatocellular carcinoma and its microenvironment. A: Hepatocellular carcinoma and its tumor microenvironment are composed of various cell populations, including differentiated cancer cells, cancer stem cells, cancer associated fibroblasts, immune and endothelial cells; B: Programmed death-1 and programmed death ligand 1 interaction and inhibition by neutralizing antibodies in tumor growth. PD-1: Programmed death-1; PD-L1: Programmed death ligand 1; CSC: Cancer stem cells; CAF: Cancer associated fibroblast; ECM: Extracellular matrix; NK: Natural killer.