Resident Macrophage-Orchestrated Immune and Fibroblast Interactions in Immune Checkpoint Inhibitor-Associated Nephrotoxicity.

ABSTRACT: Immune checkpoint inhibitors (ICIs) transform cancer therapy but are often associated with immune-related adverse events, including ICI-associated nephrotoxicity (ICI-AN). The mechanisms driving ICI-AN remain poorly understood, limiting diagnostic and therapeutic progress. This study integrates imaging mass cytometry, transcriptomics, and murine models to investigate the cellular and molecular mechanisms driving ICI-AN. Kidney biopsies from ICI-AN patients show increased resident macrophages, fibroblasts, and CD8⁺ T cells, with resident macrophages exhibiting elevated pro-inflammatory and pro-fibrotic markers. In mice, anti-PD-1 treatment induces renal injury characterized by immune cell infiltration, tubular injury, and fibrosis. Depletion of resident macrophages reduces CXCL9 and MMP12 e

SUBMITTER: Ma Y 

PROVIDER: S-EPMC12622469 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature