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整合多组学揭示了慢性淋巴细胞白血病中调节性和耗竭性T细胞格局，并确定半乳凝素-9为免疫治疗靶点。

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

作者信息

Llaó-Cid L, Wong Jkl, Fernandez Botana I, Paul Y, Wierz M, Pilger L-M, Floerchinger A, Tan C L, Gonder S, Pagano G, Chazotte M, Bestak K, Schifflers C, Iskar M, 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 W, Dietrich S, Lichter P, Moussay E, Paggetti J, Zapatka M, Seiffert M

机构信息

Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Tumor Stroma Interactions, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg.

出版信息

Nat Commun. 2025 Aug 7;16(1):7271. doi: 10.1038/s41467-025-61822-x.

DOI:10.1038/s41467-025-61822-x
PMID:40775219
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12331977/
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 (T) and terminally exhausted (T) 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.

摘要

T细胞耗竭导致慢性淋巴细胞白血病（CLL）免疫治疗失败。在此，我们使用单细胞RNA测序、质谱流式细胞术和组织成像技术，分析了CLL患者血液、骨髓和淋巴结以及CLL小鼠模型中的T细胞。CLL淋巴结中的T细胞表现出最明显的特征，包括调节性T细胞和处于各种耗竭状态的CD8 T细胞（包括前体耗竭T细胞和终末耗竭T细胞）的积累。T细胞受体测序数据的整合以及predicTCR分类器的使用表明，淋巴结中富含CLL反应性T细胞。相互作用组研究揭示了潜在的免疫治疗靶点，尤其是半乳凝素-9，一种TIM3配体。在小鼠中抑制半乳凝素-9可降低疾病进展并减少TIM3+ T细胞。半乳凝素-9的表达还与CLL和其他癌症患者较差的生存率相关，表明其在免疫逃逸中的作用以及作为治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/280a9e23b2d1/41467_2025_61822_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/2bb21a43cc28/41467_2025_61822_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/f71e4336375c/41467_2025_61822_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/e20ffb8196bf/41467_2025_61822_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/74bb0b320d56/41467_2025_61822_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/db5bc2c0704f/41467_2025_61822_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/7fb242194c7c/41467_2025_61822_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/610eff0415d3/41467_2025_61822_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/280a9e23b2d1/41467_2025_61822_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/2bb21a43cc28/41467_2025_61822_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/f71e4336375c/41467_2025_61822_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/e20ffb8196bf/41467_2025_61822_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/74bb0b320d56/41467_2025_61822_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/db5bc2c0704f/41467_2025_61822_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/7fb242194c7c/41467_2025_61822_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/610eff0415d3/41467_2025_61822_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/158c/12331977/280a9e23b2d1/41467_2025_61822_Fig8_HTML.jpg

相似文献

[1]
Integrative multi-omics reveals a regulatory and exhausted T-cell landscape in CLL and identifies galectin-9 as an immunotherapy target.

Nat Commun. 2025-8-7

[2]
Multi-omics profiling identifies TNFRSF18 as a novel marker of exhausted CD8⁺ T cells and reveals tumour-immune dynamics in colorectal cancer.

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[3]
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[4]
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[6]
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[7]
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[10]
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本文引用的文献

[1]
p53 at the crossroads of tumor immunity.

Nat Cancer. 2024-7

[2]
Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target.

Blood Cancer J. 2024-5-2

[3]
Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy.

Nat Biotechnol. 2025-1

[4]
ZNF683 marks a CD8 T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome.

Cancer Cell. 2023-10-9

[5]
UnMICST: Deep learning with real augmentation for robust segmentation of highly multiplexed images of human tissues.

Commun Biol. 2022-11-18

[6]
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia.

Nat Commun. 2022-10-20

[7]
The primordial differentiation of tumor-specific memory CD8 T cells as bona fide responders to PD-1/PD-L1 blockade in draining lymph nodes.

Cell. 2022-10-27

[8]
Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data.

Nat Commun. 2022-6-9

[9]
Public T-Cell Receptors (TCRs) Revisited by Analysis of the Magnitude of Identical and Highly-Similar TCRs in Virus-Specific T-Cell Repertoires of Healthy Individuals.

Front Immunol. 2022

[10]
Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target.

Nat Commun. 2022-2-9

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