Introduction.- Molecular and cellular functions of CTLA-4 pathway.- Roles of PD-1/PD-L1 pathway: signaling, cancer, and beyond.- Discovery of new immune checkpoints: family grows up.- Mechanisms of resistance to checkpoint blockade therapy.- Molecular events behind adverse effects.- Rational discovery of response biomarkers.- Spatiotemporal changes in checkpoint molecule expression.- Functions of checkpoint molecules beyond immune evasion.- Genetic alterations and checkpoint expression.- Regulations on messenger RNA: wires and nodes.- Folded or degraded in endoplasmic reticulum.- Mono- and poly-ubiquitination: tags for fates.- Lysosome as the black hole for checkpoint molecules.- Phosphorylation: a fast switch for checkpoint signalling.- Palmitoylation as a signal for delivery.- Checkpoints under traffic control: from and to organelles.- Exosome and secretion: action on?.- Macromolecules and antibody-based drugs.- Mechanisms inspired targeting peptides.- Small molecular inhibitors.- Therapeutic development of immune checkpoint blockers.- Concluding remarks
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