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: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
07 August 2025
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| 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 
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| 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 |
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| 245 | 1 | 0 | |a Integrative multi-omics reveals a regulatory and exhausted T-cell landscape in CLL and identifies galectin-9 as an immunotherapy target |c 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 |
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| 520 | |a 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. | ||
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