Journal Article

DKFZ-2025-01646

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Integrative multi-omics reveals a regulatory and exhausted T-cell landscape in CLL and identifies galectin-9 as an immunotherapy target.

Llaó-Cid, L. (First author)DKFZ* ; Wong, J. (First author)DKFZ* ; Fernandez Botana, I. ; Paul, Y. ; Wierz, M.DKFZ* ; Pilger, L.-M.DKFZ* ; Floerchinger, A.DKFZ* ; Tan, C. L.DKFZ* ; Gonder, S. ; Pagano, G. ; Chazotte, M. ; Bestak, K. ; Schifflers, C.DKFZ* ; Iskar, M.DKFZ* ; Roider, T. ; Czernilofsky, F. ; Bruch, P.-M. ; Mallm, J. P. ; Cosma, A. ; Campton, D. E. ; Gerhard-Hartmann, E. ; Rosenwald, A. ; Colomer, D. ; Campo, E. ; Schapiro, D. ; Green, E.DKFZ* ; Dietrich, S. ; Lichter, P.DKFZ* ; Moussay, E. ; Paggetti, J. ; Zapatka, M. (Last author)DKFZ* ; Seiffert, M. (Last author)DKFZ*

2025
Springer Nature [London]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s41467-025-61822-x

Abstract: 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.

Keyword(s): Galectins: metabolism (MeSH) ; Galectins: genetics (MeSH) ; Galectins: antagonists & inhibitors (MeSH) ; Galectins: immunology (MeSH) ; Leukemia, Lymphocytic, Chronic, B-Cell: immunology (MeSH) ; Leukemia, Lymphocytic, Chronic, B-Cell: therapy (MeSH) ; Leukemia, Lymphocytic, Chronic, B-Cell: genetics (MeSH) ; Leukemia, Lymphocytic, Chronic, B-Cell: pathology (MeSH) ; Humans (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; Hepatitis A Virus Cellular Receptor 2: metabolism (MeSH) ; Immunotherapy: methods (MeSH) ; T-Lymphocytes, Regulatory: immunology (MeSH) ; T-Lymphocytes, Regulatory: metabolism (MeSH) ; Lymph Nodes: immunology (MeSH) ; Lymph Nodes: pathology (MeSH) ; CD8-Positive T-Lymphocytes: immunology (MeSH) ; CD8-Positive T-Lymphocytes: metabolism (MeSH) ; Female (MeSH) ; Male (MeSH) ; Disease Models, Animal (MeSH) ; Multiomics (MeSH) ; Galectins ; LGALS9 protein, human ; Hepatitis A Virus Cellular Receptor 2 ; galectin 9, mouse ; HAVCR2 protein, human

Note: #EA:B060#LA:B060#

---

Contributing Institute(s):

1. B060 Molekulare Genetik (B060)
2. KKE Neuroimmunologie und Hirntumorimmunologie (D170)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

---

Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---