Osteoarthritis increases the risk of inflammatory arthritis due to immune checkpoint inhibitors associated with tissue-resident memory T cells

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(3), P. e010758 - e010758

Published: March 1, 2025

Objective Immune checkpoint inhibitors (ICIs) have significantly advanced cancer treatment, but they can also lead to immune-related adverse events (irAEs), including inflammatory arthritis. Understanding the risk factors and underlying mechanisms of irAE pathogenesis is crucial for optimal patient management. Increasing evidence suggests that ICI-mediated activation tissue-resident memory T cells (T RM ) eliminates associated with irAE-related colitis dermatitis. However, it remains unknown why development these irAEs restricted a subset patients. We hypothesized osteoarthritis (OA) tissue damage chronic inflammation recruitment differentiation joint cells, predisposing individuals ICI-induced Methods Using comprehensive approach, we compared prevalence OA in patients irAE-arthritis those non-arthritis without irAEs. Additionally, used immunophenotyping techniques characterize T-cell populations blood synovial fluid irAE-arthritis. Results Our findings revealed higher who developed than controls. Furthermore, multivariable analysis identified OA, body mass index, smoking as independent expressing programmed cell death protein-1 (PD-1) were predominant joints. These directly targeted by ICIs, resulting an immune response transition from Conclusion This study, first its kind, identifies significant factor irAEarthritis. It reveals potential mechanism which ICIs activate PD-1-positive joints, research could enhance management treatment receiving ICIs.

Language: Английский

The joint accumulation hypothesis in arthritis

Seminars in Arthritis and Rheumatism, Journal Year: 2025, Volume and Issue: unknown, P. 152685 - 152685

Published: Feb. 1, 2025

Language: Английский

5’ HOXD GENES DIFFERENTIALLY REGULATE GENE EXPRESSION OF SYNOVIAL FIBROBLASTS IN HAND JOINTS

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 12, 2024

ABSTRACT We previously demonstrated that Homeobox (HOX) transcription factors are differentially expressed between joint locations and can accurately assign synovial fibroblasts (SFs) to their correct location. show here the expression of 5’HOXD HOXD10, HOXD11, HOXD13 in SFs strikingly overlaps with predilection sites for development rheumatoid arthritis (RA). Changes gene after silencing 5’HOXDs aligned joint-specific differences RA SFs. In particular, we identify as regulator or primary cilia function modulating cell cycle, DNA damage proteasome activity. Accordingly, specific morphology, repair thus propose play a role shaping functions might underlie pathognomic pattern involvement RA.

Language: Английский