Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors

Shoiab Bukhari, Brian S. Henick, Robert J. Winchester, Shalom Lerrer, Kieran Adam, Yevgeniya Gartshteyn, Rohan Maniar, Ziyan Lin, Alireza Khodadadi-Jamayran, Aristotelis Tsirigos, Mary M. Salvatore, Galina G. Lagos, Steven L. Reiner, Matthew C. Dallos, Matthen Mathew, Naiyer A. Rizvi, Adam Mor

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

PD-1 is an inhibitory receptor in T cells, and antibodies that block its interaction with ligands augment anti-tumor immune responses. The clinical potential of these agents is limited by the fact that half of all patients develop immune-related adverse events (irAEs). To generate insights into the cellular changes that occur during anti-PD-1 treatment, we performed single-cell RNA sequencing of circulating T cells collected from patients with cancer. Using the K-nearest-neighbor-based network graph-drawing layout, we show the involvement of distinctive genes and subpopulations of T cells. We identify that at baseline, patients with arthritis have fewer CD8 TCM cells, patients with pneumonitis have more CD4 TH2 cells, and patients with thyroiditis have more CD4 TH17 cells when compared with patients who do not develop irAEs. These data support the hypothesis that different populations of T cells are associated with different irAEs and that characterization of these cells’ pre-treatment has the potential to serve as a toxicity-specific predictive biomarker.

Original languageEnglish
Article number100868
JournalCell Reports Medicine
Volume4
Issue number1
DOIs
StatePublished - 17 Jan 2023
Externally publishedYes

Keywords

  • PD-1
  • T cells
  • arthritis
  • autoimmunity
  • checkpoint inhibitor
  • immune-related adverse events
  • irAEs
  • pneumonitis
  • single-cell RNA sequencing
  • thyroiditis

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