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Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma

Author

Listed:
  • Min Liu

    (National University of Singapore
    Chongqing University Cancer Hospital
    Tianjin Medical University Cancer Institute and Hospital)

  • Giorgio Bertolazzi

    (University of Palermo
    University of Palermo)

  • Shruti Sridhar

    (National University of Singapore)

  • Rui Xue Lee

    (National University of Singapore)

  • Patrick Jaynes

    (National University of Singapore)

  • Kevin Mulder

    (Technology and Research
    Equipe Labellisée—Ligue Nationale contre le Cancer
    Université Paris-Saclay, Gustave Roussy)

  • Nicholas Syn

    (National University of Singapore
    National University of Singapore)

  • Michal Marek Hoppe

    (National University of Singapore)

  • Shuangyi Fan

    (National University of Singapore)

  • Yanfen Peng

    (National University of Singapore)

  • Jocelyn Thng

    (National University of Singapore)

  • Reiya Chua

    (National University Health System)

  • Jayalakshmi

    (National University Health System)

  • Yogeshini Batumalai

    (National University Health System)

  • Sanjay De Mel

    (National University Health System
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Limei Poon

    (National University Health System
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Esther Hian Li Chan

    (National University Health System
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Joanne Lee

    (National University Health System
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Susan Swee-Shan Hue

    (National University of Singapore
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Sheng-Tsung Chang

    (Chi-Mei Medical Center)

  • Shih-Sung Chuang

    (Chi-Mei Medical Center)

  • K. George Chandy

    (Nanyang Technological University Singapore)

  • Xiaofei Ye

    (Kindstar Global Precision Medicine Institute)

  • Qiang Pan-Hammarström

    (Karolinska Institutet)

  • Florent Ginhoux

    (Technology and Research
    Equipe Labellisée—Ligue Nationale contre le Cancer
    Université Paris-Saclay, Gustave Roussy)

  • Yen Lin Chee

    (National University Health System
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Siok-Bian Ng

    (National University of Singapore
    National University of Singapore
    Yong Loo Lin School of Medicine, National University of Singapore)

  • Claudio Tripodo

    (University of Palermo
    Histopathology Unit, Institute of Molecular Oncology Foundation (IFOM) ETS - The AIRC Institute of Molecular Oncology)

  • Anand D. Jeyasekharan

    (National University of Singapore
    National University Health System
    Yong Loo Lin School of Medicine, National University of Singapore
    National University of Singapore)

Abstract

Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digital spatial profiling with whole transcriptome analysis of CD68+ cells, we characterize macrophages in distinct spatial niches of reactive lymphoid tissues (RLTs) and DLBCL. We reveal transcriptomic differences between macrophages within RLTs (light zone /dark zone, germinal center/ interfollicular), and between disease states (RLTs/ DLBCL), which we then use to generate six spatially-derived macrophage signatures (MacroSigs). We proceed to interrogate these MacroSigs in macrophage and DLBCL single-cell RNA-sequencing datasets, and in gene-expression data from multiple DLBCL cohorts. We show that specific MacroSigs are associated with cell-of-origin subtypes and overall survival in DLBCL. This study provides a spatially-resolved whole-transcriptome atlas of macrophages in reactive and malignant lymphoid tissues, showing biological and clinical significance.

Suggested Citation

  • Min Liu & Giorgio Bertolazzi & Shruti Sridhar & Rui Xue Lee & Patrick Jaynes & Kevin Mulder & Nicholas Syn & Michal Marek Hoppe & Shuangyi Fan & Yanfen Peng & Jocelyn Thng & Reiya Chua & Jayalakshmi &, 2024. "Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46220-z
    DOI: 10.1038/s41467-024-46220-z
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    References listed on IDEAS

    as
    1. Ash A. Alizadeh & Michael B. Eisen & R. Eric Davis & Chi Ma & Izidore S. Lossos & Andreas Rosenwald & Jennifer C. Boldrick & Hajeer Sabet & Truc Tran & Xin Yu & John I. Powell & Liming Yang & Gerald E, 2000. "Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling," Nature, Nature, vol. 403(6769), pages 503-511, February.
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