Immune checkpoint inhibitor-associated inflammatory arthritis - PubMed
3 days ago
- #autoimmunity
- #immune checkpoint inhibitors
- #inflammatory arthritis
- Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy by targeting immune checkpoints like PD-1 and CTLA-4.
- ICI treatment is associated with autoimmune side effects, including inflammatory arthritis (ICI-IA), occurring in ~6% of patients.
- ICI-IA resembles rheumatoid arthritis but is usually seronegative, with joint inflammation detectable via imaging even without swelling.
- The synovium in ICI-IA shows clonal expansion of CD38hiCD127-CD8+ T cells and IL-1βhi macrophages, communicating via CXCL10-CXCR3 and CCR1-CCL3/5 pathways.
- Activation of naïve CD4+ T cells and impaired Tregs exacerbate ICI-IA, especially with combination ICI therapy (anti-CTLA-4 plus anti-PD-1).
- ICI-IA provides insights into mechanisms of other inflammatory arthritis forms and suggests future research directions.