Immune checkpoints (ICs) play a central role in maintaining immune homoeostasis. The discovery that tumours use this physiological mechanism to avoid elimination by the immune system, opened up avenues for therapeutic targeting of ICs as a novel way of treating cancer. However, this therapy a new array of autoimmune side effects, termed immune-related adverse events (irAEs). In this narrative review, we first recapitulate the physiological function of ICs that are approved targets for cancer immunotherapy (CTLA-4, PD-(L)1 and LAG-3), as the groundwork to critically discuss current knowledge on irAEs. Specifically, we summarize clinical aspects and examine a molecular classification and predisposing factors of irAEs. Finally, we discuss irAE treatment, particularly emphasizing how molecular knowledge is changing the current treatment paradigm.
Keywords: B-cell; CTLA-4; Complement; Cytokine; Cytokine therapy; Cytotoxic T-lymphocyte-associated protein 4; Immune-related adverse event; IrAE; LAG-3; Lymphocyte-activation gene 3; PD-1; PD-L1; Programmed cell death protein 1; Programmed death-ligand 1; T-cell.
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