Universität zu Köln

Huuhtanen, Jani ORCID: 0000-0003-2750-4033, Bhattacharya, Dipabarna ORCID: 0000-0002-0808-7783, Lonnberg, Tapio ORCID: 0000-0003-4484-5657, Kankainen, Matti, Kerr, Cassandra, Theodoropoulos, Jason, Rajala, Hanna ORCID: 0000-0003-2675-2385, Gurnari, Carmelo ORCID: 0000-0001-6829-5544, Kasanen, Tiina, Braun, Till, Teramo, Antonella, Zambello, Renato, Herling, Marco, Ishida, Fumihiro, Kawakami, Toru ORCID: 0000-0003-0178-5332, Salmi, Marko, Loughran, Thomas, Maciejewski, Jaroslaw P., Lahdesmaki, Harri, Kelkka, Tiina ORCID: 0000-0003-1085-6382 and Mustjoki, Satu ORCID: 0000-0002-0816-8241 (2022). Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8(+) T-cell large granular lymphocytic leukemia. Nat. Commun., 13 (1). BERLIN: NATURE PORTFOLIO. ISSN 2041-1723

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Abstract

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+TCR alpha beta-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 IFN gamma. 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Huuhtanen, Jani UNSPECIFIED orcid.org/0000-0003-2750-4033 UNSPECIFIED Bhattacharya, Dipabarna UNSPECIFIED orcid.org/0000-0002-0808-7783 UNSPECIFIED Lonnberg, Tapio UNSPECIFIED orcid.org/0000-0003-4484-5657 UNSPECIFIED Kankainen, Matti UNSPECIFIED UNSPECIFIED UNSPECIFIED Kerr, Cassandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Theodoropoulos, Jason UNSPECIFIED UNSPECIFIED UNSPECIFIED Rajala, Hanna UNSPECIFIED orcid.org/0000-0003-2675-2385 UNSPECIFIED Gurnari, Carmelo UNSPECIFIED orcid.org/0000-0001-6829-5544 UNSPECIFIED Kasanen, Tiina UNSPECIFIED UNSPECIFIED UNSPECIFIED Braun, Till UNSPECIFIED UNSPECIFIED UNSPECIFIED Teramo, Antonella UNSPECIFIED UNSPECIFIED UNSPECIFIED Zambello, Renato UNSPECIFIED UNSPECIFIED UNSPECIFIED Herling, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Ishida, Fumihiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Kawakami, Toru UNSPECIFIED orcid.org/0000-0003-0178-5332 UNSPECIFIED Salmi, Marko UNSPECIFIED UNSPECIFIED UNSPECIFIED Loughran, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Maciejewski, Jaroslaw P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lahdesmaki, Harri UNSPECIFIED UNSPECIFIED UNSPECIFIED Kelkka, Tiina UNSPECIFIED orcid.org/0000-0003-1085-6382 UNSPECIFIED Mustjoki, Satu UNSPECIFIED orcid.org/0000-0002-0816-8241 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-692940
DOI:	10.1038/s41467-022-29173-z
Journal or Publication Title:	Nat. Commun.
Volume:	13
Number:	1
Date:	2022
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	2041-1723
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SOMATIC STAT3 MUTATIONS; PATHOGENESIS; EXPRESSION; THERAPY; CYTOMEGALOVIRUS; ASSOCIATION; RESPONSES; PACKAGE Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69294