Immune hallmarks of recurrent immune checkpoint inhibitor-mediated inflammatory arthritis

Ninety three percent and fifty percent of the top ten expanded clones of effector CD8+ T cells and PD-1hi CXCL13hi CD4+ T cells, respectively, were shared between the first and second ICI-IA flare. These top clones were characterized by the production of pro-inflammatory type 1 cytokines including IFNg, TNFa, and IL-21, especially in the second flare, suggesting immune memory responses to cognate antigen. Cell-cell communication analysis suggests that effector CD8+ T cells and PD-1hi CXCL13hi CD4+ T cells interacted with each other and with myeloid cells and B cells through chemokines (CXCL9/10/11/13, CCL3) and cytokines (MIF, IL-2/7/15/21).

Overall, longitudinal SF analysis from ICI-IA patients for the first time revealed the expansion of effector CD8+ T cells and PD-1hi CXCL13hi CD4+ T cells with type 1 cytokine signatures that potentially contribute to development or recurrence of ICI-IA.