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

• Published in: Cell reports. Medicine 2023-01, Vol.4 (1), p.100868, Article 100868
• Main Authors: Bukhari, Shoiab, Henick, Brian S., Winchester, Robert J., Lerrer, Shalom, Adam, Kieran, Gartshteyn, Yevgeniya, Maniar, Rohan, Lin, Ziyan, Khodadadi-Jamayran, Alireza, Tsirigos, Aristotelis, Salvatore, Mary M., Lagos, Galina G., Reiner, Steven L., Dallos, Matthew C., Mathew, Matthen, Rizvi, Naiyer A., Mor, Adam
• Format: Article
• Language: English
• Subjects: arthritis; autoimmunity; checkpoint inhibitor; Humans; immune-related adverse events; Immunity; Immunotherapy - adverse effects; irAEs; Neoplasms - drug therapy; Neoplasms - genetics; PD-1; pneumonitis; Sequence Analysis, RNA; single-cell RNA sequencing; T cells; T-Lymphocytes; thyroiditis
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2022.100868

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. [Display omitted] •Selected T cell subsets are associated with organ-specific immune-related adverse events•Patients with immune-related arthritis have lower levels of CD8 TCM cells at baseline•Patients with immune-related pneumonitis have more CD4 TH2 cells at baseline•Patients with immune-related thyroiditis have more CD4 TH17 cells at baseline Bukhari et al. report that different subsets of T cells are associated with organ-specific immune-related adverse events of checkpoint inhibitors and that quantification and characterization of these populations of cells pre-treatment have the potential to serve as toxicity-specific predictive biomarkers.