| Autor: |
Huuhtanen, Jani, Bhattacharya, Dipabarna, Lönnberg, Tapio, Kankainen, Matti, Kerr, Cassandra, Theodoropoulos, Jason, Rajala, Hanna, Gurnari, Carmelo, Kasanen, Tiina, Braun, Till, Teramo, Antonella, Zambello, Renato, Herling, Marco, Ishida, Fumihiro, Kawakami, Toru, Salmi, Marko, Loughran, Thomas, Maciejewski, Jaroslaw P., Lähdesmäki, Harri, Kelkka, Tiina |
| Předmět: |
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| Zdroj: |
Nature Communications; 4/11/2022, Vol. 13 Issue 1, p1-16, 16p |
| Abstrakt: |
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. T cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder involving clonally expanded T cell clones and is not fully understood. Here the authors show that the rest of the immune repertoire is interconnected with the T-LGLL clonotype(s) and is more mature, cytotoxic and clonally restricted than in other cancers and autoimmune disorders. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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