Toxicity patterns with immunomodulating antibodies and their combinations.

Immune checkpoint molecules cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1), but also LAG-3 and TIM-3, are involved in regulation of peripheral tolerance in order to prevent autoimmunity. Blocking of these cell surface proteins by antibodies has resulted in remarkable anti-tumor immunity; however this immunity is accompanied by immune-related adverse reactions (irAEs), resembling autoimmune diseases. Hence, treatment with immunosuppressive drugs is highly effective and resolves the symptoms caused by these adverse events rapidly. In this review, toxicity patterns observed with immune checkpoint blockade are described for single-agent and combination treatments.