Single-cell profiling identifies IL1B^hi macrophages associated with inflammation in PD-1 inhibitor-induced...

Inflammatory arthritis (IA) is a common rheumatic adverse event following immune checkpoint inhibitors treatment. The clinical disparities between IA and rheumatoid arthritis (RA) imply disease heterogeneity and distinct mechanisms, which remain elusive. Here, we profile CD45⁺ cells from the peripheral blood or synovial fluid (SF) of patients with PD-1-induced IA (PD-1-IA) or RA using single-cell RNA sequencing. We report the predominant expansion of IL1B^hi myeloid cells with enhanced NLRP3 inflammasome activity, in both the SF and peripheral blood of PD-1-IA, but not RA. IL1B^hi macrophages in the SF of PD-1-IA shared similar inflammatory signatures and might originate from peripheral IL1B^hi monocytes. Exhausted CD8⁺ T cells (Texs) significantly accumulated in the SF of patients with PD-1-IA. IL1B^hi myeloid cells communicated with CD8⁺ Texs possibly via the CCR1-CCL5/CCL3 and CXCL10-CXCR3 axes. Collectively, these results demonstrate different cellular and molecular pathways in PD-1-IA and RA and highlight IL1B^hi macrophages as a possible therapeutic target in PD-1-IA.