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Integrative multi-omics reveals a regulatory and exhausted T-cell landscape in CLL and identifies galectin-9 as an immunotherapy target

T-cell exhaustion contributes to immunotherapy failure in chronic lymphocytic leukemia (CLL). Here, we analyze T cells from CLL patients’ blood, bone marrow, and lymph nodes, as well as from a CLL mouse model, using single-cell RNA sequencing, mass cytometry, and tissue imaging. T cells in CLL lymph...

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Hauptverfasser: Llaó Cid, Laura (VerfasserIn) , Wong, J. K. L. (VerfasserIn) , Fernandez Botana, I. (VerfasserIn) , Paul, Yashna (VerfasserIn) , Wierz, M. (VerfasserIn) , Pilger, Liesa-Marie (VerfasserIn) , Floerchinger, Alessia (VerfasserIn) , Tan, Chin Leng (VerfasserIn) , Gonder, S. (VerfasserIn) , Pagano, G. (VerfasserIn) , Chazotte, Margot (VerfasserIn) , Bestak, Kresimir (VerfasserIn) , Schifflers, C. (VerfasserIn) , Iskar, M. (VerfasserIn) , Roider, Tobias (VerfasserIn) , Czernilofsky, Felix (VerfasserIn) , Bruch, Peter-Martin (VerfasserIn) , Mallm, Jan-Philipp (VerfasserIn) , Cosma, A. (VerfasserIn) , Campton, D. E. (VerfasserIn) , Gerhard-Hartmann, E. (VerfasserIn) , Rosenwald, A. (VerfasserIn) , Colomer, D. (VerfasserIn) , Campo, E. (VerfasserIn) , Schapiro, Denis (VerfasserIn) , Green, Edward W. (VerfasserIn) , Dietrich, Sascha (VerfasserIn) , Lichter, Peter (VerfasserIn) , Moussay, E. (VerfasserIn) , Paggetti, J. (VerfasserIn) , Zapatka, Marc (VerfasserIn) , Seiffert, M. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 07 August 2025
In: Nature Communications
Year: 2025, Jahrgang: 16, Pages: 1-22
ISSN:2041-1723
DOI:10.1038/s41467-025-61822-x
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-025-61822-x
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-025-61822-x
Volltext
Verfasserangaben:L. Llaó-Cid, J.K.L. Wong, I. Fernandez Botana, Y. Paul, M. Wierz, L.-M. Pilger, A. Floerchinger, C.L. Tan, S. Gonder, G. Pagano, M. Chazotte, K. Bestak, C. Schifflers, M. Iskar, T. Roider, F. Czernilofsky, P.-M. Bruch, J.P. Mallm, A. Cosma, D.E. Campton, E. Gerhard-Hartmann, A. Rosenwald, D. Colomer, E. Campo, D. Schapiro, E.W. Green, S. Dietrich, P. Lichter, E. Moussay, J. Paggetti, M. Zapatka & M. Seiffert
Beschreibung
Zusammenfassung:T-cell exhaustion contributes to immunotherapy failure in chronic lymphocytic leukemia (CLL). Here, we analyze T cells from CLL patients’ blood, bone marrow, and lymph nodes, as well as from a CLL mouse model, using single-cell RNA sequencing, mass cytometry, and tissue imaging. T cells in CLL lymph nodes show the most distinct profiles, with accumulation of regulatory T cells and CD8+ T cells in various exhaustion states, including precursor (TPEX) and terminally exhausted (TEX) cells. Integration of T-cell receptor sequencing data and use of the predicTCR classifier suggest an enrichment of CLL-reactive T cells in lymph nodes. Interactome studies reveal potential immunotherapy targets, notably galectin-9, a TIM3 ligand. Inhibiting galectin-9 in mice reduces disease progression and TIM3+ T cells. Galectin-9 expression also correlates with worse survival in CLL and other cancers, suggesting its role in immune evasion and potential as a therapeutic target.
Beschreibung:Online veröffentlicht: 07. August 2025
Gesehen am 21.01.2026
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-025-61822-x

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