# Understanding the Inflammatory Aspect of Osteoarthritis: Lessons from Immune Checkpoint Inhibitors

## TL;DR

This review explores how insights from cancer immunotherapy reveal an inflammatory component in osteoarthritis, suggesting new treatment approaches.

## Contribution

The paper highlights the role of immune checkpoint inhibitors in uncovering inflammation in osteoarthritis and proposes new therapeutic strategies.

## Key findings

- Osteoarthritis has an inflammatory component involving immune cells in joint tissue.
- Immunosuppressive therapies show potential in modifying osteoarthritis progression.
- Immune checkpoint inhibitors can trigger arthritis as an adverse event, indicating immune involvement in OA.

## Abstract

Osteoarthritis (OA) is the most prevalent form of arthritis and is a major global health burden. OA is a heterogeneous condition with multiple contributing mechanisms that characterize different subtypes and stages of the disease. In this review, we examine the insights gained into the immunological characteristics of OA that have emerged from the increasingly widespread use of checkpoint inhibitors in the immunotherapy of malignancies. We discuss how the conventional view of OA as a degenerative disease is changing in view of the evidence suggesting that OA has an inflammatory component along with the presence in joint tissue of peripherally tolerized autoreactive resident memory T cells, which upon release of their inhibition by immunotherapy mediate immune-related adverse event arthritis (irAE-arthritis). We review clinical trials evaluating the efficacy of immunosuppressive therapies in modifying the course of OA, thereby providing an additional perspective on the presence and nature of the inflammation in OA. In summary, we argue that a shift from the traditional understanding of OA as a mechanical disease to one that incorporates the role of synovial immune cells and mechanisms of self-tolerance is necessary to guide future therapies, including the use of immune checkpoints for patients with OA.