Urinary T cells are detected in patients with immune checkpoint inhibitor-associated immune nephritis that are clonotypically identical to kidney T cell infiltrates

Oncoimmunology. 2022 Sep 22;11(1):2124678. doi: 10.1080/2162402X.2022.2124678. eCollection 2022.

Abstract

Acute kidney injury (AKI) occurs in ~20% of patients receiving immune checkpoint inhibitor (ICI) therapy; however, only 2-5% will develop ICI-mediated immune nephritis. Conventional tests are nonspecific in diagnosing disease pathology and invasive procedures (i.e. kidney biopsy) may not be feasible. In other autoimmune renal diseases, urinary immune cells correlated with the pathology or were predictive of disease activity. Corresponding evidence and analysis are absent for ICI-mediated immune nephritis. We report the first investigation analyzing immune cell profiles of matched kidney biopsies and urine of patients with ICI-AKI. We demonstrated the presence of urinary T cells in patients with immune nephritis by flow cytometry analysis. Clonotype analysis of T cell receptor (TCR) sequences confirmed enrichment of kidney TCRs in urine. As ICI therapies become standard of care for more cancers, noninvasively assessing urinary immune cells of ICI therapy recipients can facilitate clinical management and an opportunity to tailor ICI-nephritis treatment.

Keywords: Immune checkpoint inhibitor; T cell receptor clonotype; acute interstitial nephritis; acute kidney injury; immune nephritis; immune-related adverse event; urinary immune cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / diagnosis
  • Acute Kidney Injury* / drug therapy
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Kidney / pathology
  • Nephritis* / chemically induced
  • Nephritis* / diagnosis
  • Nephritis* / drug therapy
  • T-Lymphocytes

Substances

  • Immune Checkpoint Inhibitors