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Immune checkpoint inhibitors (ICI) are remarkable agents that represent a revolutionary approach to treat cancer. Rather than directly killing tumour cells, ICIs inhibit the regulatory pathways that prevent a T cell response to the tumour. With checkpoints blocked and T cells free to act, the tumour becomes a target for cytotoxic T cells. ICIs interdict key costimulatory systems involved in checkpoint regulation, binding to either cytotoxic T lymphocyte associated antigen 4 (CTLA-4) or the programme cell death 1 (PD-1) molecule or its ligand, PD-1L. These antibodies can be used either alone or in combination.1
In view of the effects of ICIs on T cell regulation, this form of therapy is associated with considerable toxicity and a wide variety of immune-related adverse events (irAE). The nature and frequency of these effects vary among agents and include effects on the gastrointestinal tract (colitis), liver, lung (pneumonitis), skin (rash and pruritus) and endocrine glands including hypophysitis. Since CTLA-4 and PD-1 systems involve different lymphocyte populations and act at different sites, the combination shows a broader range of side effects and an increasing frequency.2
For the rheumatologist, the use of …
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.
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