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The PD-1:PD-L1 axis in Inflammatory Arthritis
Mary Canavan1,2, Achilleas Floudas3,4, Douglas J Veale4
1Department of Molecular Rheumatology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland. mary.canavan3@gmail.com.
Abstract:
The activation of antigen specific T cells during an immune response is a tightly regulated process at the level of both costimulatory and coinhibitory receptors. One such coinhibitory receptor or checkpoint inhibitor which has received much attention in the field of oncology is the programmed cell death protein 1 (PD-1). Blockade of PD-1 or its ligand PD-L1 has proven successful in the treatment of a wide variety of cancers, therefore highlighting an important role for this pathway in anti-tumour immune responses. However, a caveat of PD-1 therapy and boosting anti-tumour immune responses is the development of self-reactive T cells which can lead to the induction of various autoimmune or inflammatory diseases, referred to as immune- related adverse events (irAEs). The emergence of rheumatological irAEs such as Inflammatory Arthritis (IA) in recent years has highlighted the importance of PD-1 in maintaining self-tolerance. Furthermore, the emergence of rheumatology related irAEs raises an important question as to how defects in this pathway can contribute to spontaneous rheumatological disease. In this review, we describe the biological distribution, function and regulation of the PD-1 pathway, its potential role in IA and irAE related IA.
Insights
Programmed cell death protein 1 (PD-1) regulates T cells. While PD-1 blockade treats cancer, it can cause autoimmune diseases like inflammatory arthritis by impairing self-tolerance.
Area of Science:
- Immunology
- Oncology
- Rheumatology
Background:
- T cell activation involves costimulatory and coinhibitory receptors.
- Programmed cell death protein 1 (PD-1) is a key coinhibitory receptor, crucial in oncology.
- PD-1/PD-L1 pathway blockade is effective in cancer treatment but can cause immune-related adverse events (irAEs).
Purpose of the Study:
- To review the biological distribution, function, and regulation of the PD-1 pathway.
- To explore the role of PD-1 in inflammatory arthritis (IA) and IA-related irAEs.
- To understand how PD-1 pathway defects contribute to spontaneous rheumatological diseases.
Main Methods:
- Literature review of PD-1 pathway biology.
- Analysis of PD-1's role in anti-tumour immunity.
- Investigation of PD-1's involvement in self-tolerance and autoimmune diseases.
Main Results:
- PD-1 blockade enhances anti-tumour immunity but can lead to self-reactive T cells.
- Emerging rheumatological irAEs, like IA, highlight PD-1's role in maintaining self-tolerance.
- Defects in the PD-1 pathway are implicated in the development of spontaneous rheumatological conditions.
Conclusions:
- The PD-1 pathway is critical for balancing anti-tumour immunity and self-tolerance.
- Understanding PD-1's role in IA and irAEs is essential for managing autoimmune side effects of cancer immunotherapy.
- Further research into PD-1 pathway defects may reveal mechanisms underlying rheumatological diseases.
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