Predominant CD8+ cell infiltration and low accumulation of regulatory T cells in immune checkpoint inhibitor‐induced tubulointerstitial nephritis

Abstract

Immune checkpoint inhibitors (ICIs) can provide survival benefits to cancer patients; however, they sometimes result in the development of renal immune‐related adverse events (irAEs). Tubulointerstitial nephritis (TIN) is the most representative pathological feature of renal irAEs. However, the clinicopathological entity and underlying pathogenesis of ICI‐induced TIN are unclear. Therefore, we compared the clinical and histological features of this condition with those of non‐ICI drug‐induced TIN. Age and C‐reactive protein levels were significantly higher in ICI‐induced TIN, but there were no significant differences in renal function. Immunophenotyping of ICI‐induced TIN showed massive T cell and macrophage infiltration with fewer B cells, plasma cells, neutrophils, and eosinophils. Compared with those in non‐ICI drug‐induced TIN, CD4+ cell numbers were significantly lower in ICI‐induced TIN but CD8+ cell numbers were not significantly different. However, CD8/CD3 and CD8/CD4 ratios were higher in ICI‐induced TIN. Moreover, CD25+ and FOXP3+ cells, namely regulatory T cells, were less abundant in ICI‐induced TIN. In conclusion, T cell, B cell, plasma cell, neutrophil, and eosinophil numbers proved useful for differentiating ICI‐induced and non‐ICI drug‐induced TIN. Furthermore, the predominant distribution of CD8+ cells and low accumulation of regulatory T cells might be associated with ICI‐induced TIN development.