Abstract: FR-OR75
Single-Cell RNA Sequencing Reveals Conserved T Cell Populations Detected across Inflamed Kidney Tissue and Urine of Patients with Immune Checkpoint Inhibitor-Associated Nephritis
Session Information
- Onconephrology: Models, Markers, and Medications
October 25, 2024 | Location: Room 33, Convention Center
Abstract Time: 04:50 PM - 05:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Mistry, Kavita, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Kernin, Isabela, Massachusetts General Hospital, Boston, Massachusetts, United States
- Smith, Neal Patrick, Massachusetts General Hospital, Boston, Massachusetts, United States
- Sun, Joie, Massachusetts General Hospital, Boston, Massachusetts, United States
- Reynolds, Kerry, Massachusetts General Hospital, Boston, Massachusetts, United States
- Gupta, Shruti, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Sise, Meghan E., Massachusetts General Hospital, Boston, Massachusetts, United States
- Villani, Alexandra-Chloe, Massachusetts General Hospital, Boston, Massachusetts, United States
Background
Immune checkpoint inhibitors inhibit the negative regulation of T cells, leading to both anti-tumor activity and immune-related adverse events such as acute interstitial nephritis (ICI-AIN). The immunologic drivers of ICI-AIN are unknown. We hypothesized that both resident and circulating CD8+ T cell subsets are present in ICI-AIN and that they are conserved across kidney tissue and the urine sediment.
Methods
To characterize the cellular populations that are enriched in ICI-AIN, we used scRNAseq to analyze epithelial and immune cells in kidney tissue and urine from a cohort of 15 patients with biopsy-proven ICI-AIN and 8 ICI-treated controls with non-AIN acute kidney injury. A total of ~200,000 cells were analyzed and revealed 23 transcriptionally distinct cell subsets, including CD8+ and CD4+ T cells, NK cells, B cells, myeloid cells, renal tubular epithelial cells, and urogenital epithelial cells.
Results
A range of T cell subsets was identified, existing on a phenotypic spectrum spanning circulation (KLF2, SELL) to residency (ITGAE), and cytotoxicity (IFNG, GZMK) to exhaustion (TIGIT). These cell subsets were conserved across both kidney tissue and urine. Gene expression analysis in ICI-AIN samples revealed populations of CD8+ T cells expressing CXCR3 and myeloid cells expressing the interferon-γ-stimulated ligands CXCL9/10, suggesting potential cell-cell interactions.
Conclusion
Taken together, our data contribute to improved understanding of the cellular perturbations in ICI-AIN and reinforce a role for the IFN-γ pathway in driving ICI-AIN. The conservation of T cell types observed across kidney tissue and urine suggests the potential for development of a non-invasive urine-based diagnostic test for ICI-AIN.
Funding
- NIDDK Support