Immune-related adverse effects of checkpoint immunotherapy and implications for the treatment of patients with cancer and autoimmune diseases

During the past decade, there has been a revolution in cancer therapeutics by the emergence of antibody-based immunotherapies that modulate immune responses against tumors. These therapies have offered treatment options to patients who are no longer responding to classic anti-cancer therapies. By blocking inhibitory signals mediated by surface receptors that are naturally upregulated during activation of antigen-presenting cells (APC) and T cells, predominantly PD-1 and its ligand PD-L1, as well as CTLA-4, such blocking agents have revolutionized cancer treatment. However, breaking these inhibitory signals cannot be selectively targeted to the tumor microenvironment (TME). Since the physiologic role of these inhibitory receptors, known as immune checkpoints (IC) is to maintain peripheral tolerance by preventing the activation of autoreactive immune cells, IC inhibitors (ICI) induce multiple types of immune-related adverse effects (irAEs). These irAEs, together with the natural properties of ICs as gatekeepers of self-tolerance, have precluded the use of ICI in patients with pre-existing autoimmune diseases (ADs). However, currently accumulating data indicates that ICI might be safely administered to such patients. In this review, we discuss mechanisms of well established and newly recognized irAEs and evolving knowledge from the application of ICI therapies in patients with cancer and pre-existing ADs.

Automated summary

In the past decade, antibody-based immunotherapies that modulate immune responses against tumors have revolutionized cancer treatment. However, these therapies have limitations due to their inability to selectively target the tumor microenvironment. Immune checkpoint inhibitors (ICI) have shown promising results in treating cancer, but their use has been limited by the occurrence of immune-related adverse effects (irAEs). Accumulating data suggests that ICI may be safely administered to patients with pre-existing autoimmune diseases (ADs). This review discusses the mechanisms of irAEs and the evolving knowledge of ICI therapy in patients with cancer and pre-existing ADs.