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@ARTICLE{LlaCid:303421,
author = {L. Llaó-Cid$^*$ and J. Wong$^*$ and I. Fernandez Botana
and Y. Paul and M. Wierz$^*$ and L.-M. Pilger$^*$ and A.
Floerchinger$^*$ and C. L. Tan$^*$ and S. Gonder and G.
Pagano and M. Chazotte and K. Bestak and C. Schifflers$^*$
and M. Iskar$^*$ and T. Roider and F. Czernilofsky and P.-M.
Bruch and J. P. Mallm and A. Cosma and D. E. Campton and E.
Gerhard-Hartmann and A. Rosenwald and D. Colomer and E.
Campo and D. Schapiro and E. Green$^*$ and S. Dietrich and
P. Lichter$^*$ and E. Moussay and J. Paggetti and M.
Zapatka$^*$ and M. Seiffert$^*$},
title = {{I}ntegrative multi-omics reveals a regulatory and
exhausted {T}-cell landscape in {CLL} and identifies
galectin-9 as an immunotherapy target.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01646},
pages = {7271},
year = {2025},
note = {#EA:B060#LA:B060#},
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.},
keywords = {Galectins: metabolism / Galectins: genetics / Galectins:
antagonists $\&$ inhibitors / Galectins: immunology /
Leukemia, Lymphocytic, Chronic, B-Cell: immunology /
Leukemia, Lymphocytic, Chronic, B-Cell: therapy / Leukemia,
Lymphocytic, Chronic, B-Cell: genetics / Leukemia,
Lymphocytic, Chronic, B-Cell: pathology / Humans / Animals /
Mice / Hepatitis A Virus Cellular Receptor 2: metabolism /
Immunotherapy: methods / T-Lymphocytes, Regulatory:
immunology / T-Lymphocytes, Regulatory: metabolism / Lymph
Nodes: immunology / Lymph Nodes: pathology / CD8-Positive
T-Lymphocytes: immunology / CD8-Positive T-Lymphocytes:
metabolism / Female / Male / Disease Models, Animal /
Multiomics / Galectins (NLM Chemicals) / LGALS9 protein,
human (NLM Chemicals) / Hepatitis A Virus Cellular Receptor
2 (NLM Chemicals) / galectin 9, mouse (NLM Chemicals) /
HAVCR2 protein, human (NLM Chemicals)},
cin = {B060 / D170},
ddc = {500},
cid = {I:(DE-He78)B060-20160331 / I:(DE-He78)D170-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40775219},
doi = {10.1038/s41467-025-61822-x},
url = {https://inrepo02.dkfz.de/record/303421},
}