Anti-PD-L1 antibodies exacerbate arthritis and pain via increased production of CXCL8/IL-8 and FGF9 in synovial fibroblasts

Immune checkpoint inhibitors (ICIs) in cancer therapy are challenged for immune-related adverse events (irAEs), such as inflammatory arthritis induced by ICI therapy (ICI-arthritis) and exacerbation of rheumatoid arthritis (RA). As well as activating T cells by inhibiting programmed cell death protein 1 (PD-1)/ programmed death ligand 1 (PD-L1) signal, anti-PD-L1 antibody (aPD-L1 ab) activate intracellular pathway through PD-L1 binding. However, the effects of aPD-L1 ab on synovial fibroblasts, which are important in the pathogenesis of arthritis, are unknown. Overall design: To assess the effect of aPD-L1 ab on synovial fibroblasts, fibroblast-like synoviocytes (RA-FLS) were collected from two RA patients and stimulated with tumor necrosis factor (TNF)-a. The cells were then stimulated with aPD-L1 ab (BioXCell) or Ctrl IgG for 24 h and total RNA was collected. The obtained total RNA was subjected to RNA-seq to examine gene expression comprehensively.