Mechanistically, ICI inhibition of CTLA-4 and PD-1/PD-L1 precipitated T-cell hyperactivation, promoting synovial lymphoplasmacytic infiltration and cytokine storms (e.g., VEGF-A-induced angiogenesis, TNF-α-driven inflammation), which contrasts with transient irAEs and resembles RA histopathology without autoantibody predominance [113]. Here, CTLA4 is linked to rheumatoid arthritis.