Peripheral B-cell receptor repertoire predicts immune-related adverse events following immune checkpoint inhibitor therapy in advanced renal cell carcinoma

Immune checkpoint inhibitor (ICI) combination therapy is effective for metastatic renal cell carcinoma (mRCC), but immune-related adverse events (irAEs) remain unpredictable. We analyzed peripheral B-cell receptor (BCR) repertoires in patients with mRCC before and 1 month after ICI initiation. BCR complementarity-determining region 3 sequences were profiled by next-generation sequencing, and immune cell composition was estimated using CIBERSORTx. Among 24 patients, 14 developed grade ≥ 3 irAEs. Patients with irAEs showed increased memory B cells and decreased naïve B cells. IgG proportion increased after ICI therapy, while IgG diversity was reduced in patients with irAEs, accompanied by expansion of dominant IgG clones. Notably, several expanded IgG clonotypes were shared exclusively among patients with irAEs. These findings suggest that early changes in the peripheral BCR repertoire may serve as surrogate biomarkers for predicting irAEs in mRCC patients receiving ICI combination therapy.