Immune checkpoint inhibitors and rheumatoid arthritis: All roads lead to PD-1?

Area of Science:

• Immunology
• Rheumatology
• Oncology

Background:

• Immune checkpoint molecules, including PD-1, PD-L1, and CTLA-4, are key regulators of immune responses.
• Immune checkpoint inhibitors (ICIs) targeting these pathways are established cancer therapies.
• Drugs that activate immune checkpoints, such as abatacept, are used for autoimmune diseases.

Purpose of the Study:

• To explore the multifaceted role of the PD-1/PD-L1 axis in rheumatology.
• To highlight the clinical relevance of PD-1/PD-L1 modulation in rheumatoid arthritis (RA).
• To identify unanswered questions in the clinical and translational research of PD-1/PD-L1 therapeutics in inflammatory arthritis.

Main Methods:

• Review of current literature on immune checkpoint inhibitors and agonists.
• Analysis of clinical scenarios involving PD-1/PD-L1 pathways in RA patients.
• Discussion of parallel development of therapeutics targeting the PD-1/PD-L1 axis.

Main Results:

• PD-1 agonists are under development for RA treatment.
• RA patients may receive ICIs for cancer, requiring rheumatologic management.
• ICI treatment can lead to new-onset inflammatory arthritis.

Conclusions:

• Modulation of the PD-1/PD-L1 axis is critical for rheumatologists in managing RA patients.
• The dual development of PD-1/PD-L1 antagonists and agonists presents unique research opportunities in inflammatory arthritis.
• Further clinical and translational research is needed to address current knowledge gaps.