Journal Article Epublish 2 citations
PubMed: 40118498 DOI: 10.1136/jitc-2024-010758
Osteoarthritis increases the risk of inflammatory arthritis due to immune checkpoint inhibitors associated with tissue-resident memory T cells.
J Immunother Cancer 13(3)
Authors: Matthieu Paiola, Daniel M Portnoy, Luke Yi Hao, Shoiab Bukhari, Robert J Winchester, Brian S Henick, Adam Mor, Yevgeniya Gartshteyn
Affiliations
- Department of Medicine, Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.
- Department of Medicine, Division of Rheumatology, Columbia University Medical Center, New York, New York, USA.
- Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.
- Department of Medicine, Division of Rheumatology, Columbia University Irving Medical Center, New York, New York, USA.
- Herbert Irvine Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, New York, USA.
- Department of Medicine, Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York, USA.
Abstract
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 of tissue-resident memory T cells (T) significantly eliminates cancer cells and is associated with irAE-related colitis and dermatitis. However, it remains unknown why the development of these irAEs is restricted to a subset of patients. We hypothesized that osteoarthritis (OA) associated tissue damage and chronic inflammation lead to the recruitment and differentiation of joint T cells, predisposing individuals to ICI-induced arthritis.
METHODS
Using a comprehensive approach, we compared the prevalence of OA in patients with irAE-arthritis to those with irAE non-arthritis and those without irAEs. Additionally, we used advanced immunophenotyping techniques to characterize T-cell populations in the blood and synovial fluid of patients with OA and irAE-arthritis.
RESULTS
Our findings revealed a significantly higher prevalence of OA in patients who developed irAE-arthritis than controls. Furthermore, the multivariable analysis identified OA, body mass index, and smoking as independent risk factors for the development of irAE-arthritis. T cells expressing programmed cell death protein-1 (PD-1) were the predominant synovial T cells in OA joints. These cells were directly targeted by ICIs, resulting in an inflammatory immune response and the transition from OA to irAE-arthritis.
CONCLUSION
This study, the first of its kind, identifies OA as a significant risk factor for irAEarthritis. It reveals a potential mechanism by which ICIs activate PD-1-positive T cells in OA joints, resulting in tissue inflammation and irAE-arthritis. This research could significantly enhance the management and treatment of patients with cancer receiving ICIs.
MeSH
Cells, Neoplasms, Arthritis, Osteoarthritis, Immunotherapy, Immune Checkpoint Inhibitors, Prevalence, Risk Factors, Therapeutics, Tissues, Memory, T-Lymphocytes