Researchers may have uncovered the immune adverse events and the specific type of CD8 T cells that characterize inflammatory arthritis induced by immune checkpoint inhibitors, according to a recent study published by Wang et al in Science Immunology.
Immune checkpoint inhibitors used to treat cancer may come with the risk of immune adverse events such as the development of arthritis, which can persist for years and require joint replacement surgery. However, little is known about the specific cells responsible for these events.
Study Methods and Results
In the new study, the researchers studied T cells from a patient with severe immune checkpoint inhibitor–associated arthritis who required bilateral knee replacement surgery. In addition to these two joint tissue samples, the researchers studied the synovial fluid of an additional 23 patients with the same condition. They then compared these samples to those from patients with rheumatoid arthritis or psoriatic arthritis. By comparing the protein and gene-expression levels across the samples, they were able to characterize the unique immunologic features of the CD8 T cells in these patients and identify that type I interferons could promote the CD8 T-cell activation seen in immune checkpoint inhibitor–associated arthritis.
The researchers discovered that the patients whose cancer was treated with immune checkpoint inhibitors had high levels of this type of CD8 T cell, and additional analyses revealed that the cells traveled between the joints and blood. Further, the CD8 T cells remained in the bloodstream, providing one explanation for why immune checkpoint inhibitor–associated arthritis may persist after immune checkpoint inhibitors are discontinued.
Conclusions
“Our results suggest that [immune checkpoint inhibitors] give rise to a unique population of CD8 T cells in patients who develop [immune checkpoint inhibitor–associated] arthritis,” emphasized co–corresponding study author Deepak A. Rao, MD, PhD, of the Division of Rheumatology, Inflammation, and Immunity at the Brigham and Women’s Hospital. “The immune events we characterized differ dramatically from the typical responses we have seen in autoimmune diseases like rheumatoid arthritis and psoriatic arthritis,” he added.
The researchers concluded that more research may be needed to characterize how the CD8 T cells may contribute to joint inflammation.
Disclosure: For full disclosures of the study authors, visit science.org.
