Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8+ T-cell large granular lymphocytic leukemia
© 2022. The Author(s)..
T cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder of mature, clonally expanded T cells, where somatic-activating STAT3 mutations are common. Although T-LGLL has been described as a chronic T cell response to an antigen, the function of the non-leukemic immune system in this response is largely uncharacterized. Here, by utilizing single-cell RNA and T cell receptor profiling (scRNA+TCRαβ-seq), we show that irrespective of STAT3 mutation status, T-LGLL clonotypes are more cytotoxic and exhausted than healthy reactive clonotypes. In addition, T-LGLL clonotypes show more active cell communication than reactive clones with non-leukemic immune cells via costimulatory cell-cell interactions, monocyte-secreted proinflammatory cytokines, and T-LGLL-clone-secreted IFNγ. Besides the leukemic repertoire, the non-leukemic T cell repertoire in T-LGLL is also more mature, cytotoxic, and clonally restricted than in other cancers and autoimmune disorders. Finally, 72% of the leukemic T-LGLL clonotypes share T cell receptor similarities with their non-leukemic repertoire, linking the leukemic and non-leukemic repertoires together via possible common target antigens. Our results provide a rationale to prioritize therapies that target the entire immune repertoire and not only the T-LGLL clonotype.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Nature communications - 13(2022), 1 vom: 11. Apr., Seite 1981 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huuhtanen, Jani [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 13.04.2022 Date Revised 22.10.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-022-29173-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM33940647X |
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| 245 | 1 | 0 | |a Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8+ T-cell large granular lymphocytic leukemia |
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| 520 | |a © 2022. The Author(s). | ||
| 520 | |a T cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder of mature, clonally expanded T cells, where somatic-activating STAT3 mutations are common. Although T-LGLL has been described as a chronic T cell response to an antigen, the function of the non-leukemic immune system in this response is largely uncharacterized. Here, by utilizing single-cell RNA and T cell receptor profiling (scRNA+TCRαβ-seq), we show that irrespective of STAT3 mutation status, T-LGLL clonotypes are more cytotoxic and exhausted than healthy reactive clonotypes. In addition, T-LGLL clonotypes show more active cell communication than reactive clones with non-leukemic immune cells via costimulatory cell-cell interactions, monocyte-secreted proinflammatory cytokines, and T-LGLL-clone-secreted IFNγ. Besides the leukemic repertoire, the non-leukemic T cell repertoire in T-LGLL is also more mature, cytotoxic, and clonally restricted than in other cancers and autoimmune disorders. Finally, 72% of the leukemic T-LGLL clonotypes share T cell receptor similarities with their non-leukemic repertoire, linking the leukemic and non-leukemic repertoires together via possible common target antigens. Our results provide a rationale to prioritize therapies that target the entire immune repertoire and not only the T-LGLL clonotype | ||
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| 700 | 1 | |a Theodoropoulos, Jason |e verfasserin |4 aut | |
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| 700 | 1 | |a Zambello, Renato |e verfasserin |4 aut | |
| 700 | 1 | |a Herling, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a Ishida, Fumihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Kawakami, Toru |e verfasserin |4 aut | |
| 700 | 1 | |a Salmi, Marko |e verfasserin |4 aut | |
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| 700 | 1 | |a Lähdesmäki, Harri |e verfasserin |4 aut | |
| 700 | 1 | |a Kelkka, Tiina |e verfasserin |4 aut | |
| 700 | 1 | |a Mustjoki, Satu |e verfasserin |4 aut | |
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