Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy.
case_series · Level IV
Where this comes from
- Record sourced from PubMed, PMID 35413951.
- Also identified by DOI 10.1038/s41467-022-29539-3 and PMC identifier 9005525.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8<sup>+</sup> T cell axis in both blood and inflamed joints. CX3CR1<sup>hi</sup> CD8<sup>+</sup> T cells in blood and CXCR3<sup>hi</sup> CD8<sup>+</sup> T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1<sup>hi</sup> CD8<sup>+</sup> T cells into joints is possibly mediated by CXCL9/10/11/16 expressed by myeloid cells. Furthermore, arthritis after combined CTLA-4 and PD-1 inhibitor therapy preferentially has enhanced Th17 and transient Th1/Th17 cell signatures. Our data provide insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.
Medical subject headings
- Arthritis
- Neoplasms