Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8+ T-cell large granular lymphocytic leukemia

Jani Huuhtanen, Dipabarna Bhattacharya, Tapio Lönnberg, Matti Kankainen, Cassandra Kerr, Jason Theodoropoulos, Hanna Rajala, Carmelo Gurnari, Tiina Kasanen, Till Braun, Antonella Teramo, Renato Zambello, Marco Herling, Fumihiro Ishida, Toru Kawakami, Marko Salmi, Thomas Loughran, Jaroslaw P. Maciejewski, Harri Lähdesmäki, Tiina KelkkaSatu Mustjoki*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

17 Citations (Scopus)
106 Downloads (Pure)


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.

Original languageEnglish
Article number1981
Pages (from-to)1-16
Number of pages16
JournalNature Communications
Issue number1
Publication statusPublished - 11 Apr 2022
MoE publication typeA1 Journal article-refereed


Dive into the research topics of 'Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8+ T-cell large granular lymphocytic leukemia'. Together they form a unique fingerprint.

Cite this