Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved..
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.
| Errataetall: |
CommentIn: Cell Rep Med. 2023 Jan 17;4(1):100902. - PMID 36652911 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:4 |
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| Enthalten in: |
Cell reports. Medicine - 4(2023), 1 vom: 17. Jan., Seite 100868 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bukhari, Shoiab [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.01.2023 Date Revised 28.03.2024 published: Print-Electronic CommentIn: Cell Rep Med. 2023 Jan 17;4(1):100902. - PMID 36652911 Citation Status MEDLINE |
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| doi: |
10.1016/j.xcrm.2022.100868 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350250871 |
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| 245 | 1 | 0 | |a Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors |
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| 500 | |a CommentIn: Cell Rep Med. 2023 Jan 17;4(1):100902. - PMID 36652911 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a PD-1 | |
| 650 | 4 | |a T cells | |
| 650 | 4 | |a arthritis | |
| 650 | 4 | |a autoimmunity | |
| 650 | 4 | |a checkpoint inhibitor | |
| 650 | 4 | |a immune-related adverse events | |
| 650 | 4 | |a irAEs | |
| 650 | 4 | |a pneumonitis | |
| 650 | 4 | |a single-cell RNA sequencing | |
| 650 | 4 | |a thyroiditis | |
| 700 | 1 | |a Henick, Brian S |e verfasserin |4 aut | |
| 700 | 1 | |a Winchester, Robert J |e verfasserin |4 aut | |
| 700 | 1 | |a Lerrer, Shalom |e verfasserin |4 aut | |
| 700 | 1 | |a Adam, Kieran |e verfasserin |4 aut | |
| 700 | 1 | |a Gartshteyn, Yevgeniya |e verfasserin |4 aut | |
| 700 | 1 | |a Maniar, Rohan |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Ziyan |e verfasserin |4 aut | |
| 700 | 1 | |a Khodadadi-Jamayran, Alireza |e verfasserin |4 aut | |
| 700 | 1 | |a Tsirigos, Aristotelis |e verfasserin |4 aut | |
| 700 | 1 | |a Salvatore, Mary M |e verfasserin |4 aut | |
| 700 | 1 | |a Lagos, Galina G |e verfasserin |4 aut | |
| 700 | 1 | |a Reiner, Steven L |e verfasserin |4 aut | |
| 700 | 1 | |a Dallos, Matthew C |e verfasserin |4 aut | |
| 700 | 1 | |a Mathew, Matthen |e verfasserin |4 aut | |
| 700 | 1 | |a Rizvi, Naiyer A |e verfasserin |4 aut | |
| 700 | 1 | |a Mor, Adam |e verfasserin |4 aut | |
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