IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-63339-9.html
   My bibliography  Save this article

Distinct cell state ecosystems for nodular lymphocyte-predominant Hodgkin lymphoma

Author

Listed:
  • Ajay Subramanian

    (Stanford University)

  • Shengqin Su

    (Stanford University)

  • Jamie Flerlage

    (University of Rochester)

  • Stefan Alig

    (Stanford University)

  • Sheren Younes

    (Stanford University)

  • Lianna J. Marks

    (Stanford University)

  • Chelsea Pinnix

    (MD Anderson Cancer Center)

  • Francisco Vega

    (MD Anderson Cancer Center)

  • Raphael Steiner

    (MD Anderson Cancer Center)

  • Priya Kumar

    (St. Jude Children’s Research Hospital)

  • Heidi Mocikova

    (Charles University)

  • Alice Sykorova

    (University Hospital and Faculty of Medicine)

  • Vit Prochazka

    (Palacky University and University Hospital Olomouc)

  • Cristiane Milito

    (Department of Pathology at the Federal University of Rio de Janeiro)

  • Pamela Allen

    (Department of Hematology & Oncology Winship Cancer Institute of Emory University)

  • Darina Paulino

    (Department of Hematology & Oncology Winship Cancer Institute of Emory University)

  • Alan Ramsay

    (University College London Hospitals NHS Foundation Trust)

  • Timothy Flerlage

    (University of Rochester)

  • Monica Palese

    (University of Rochester)

  • Robert West

    (Stanford University)

  • ChunFang Zhu

    (Stanford University)

  • Troy Noordenbos

    (Stanford University)

  • Joseph Schroers-Martin

    (Stanford University)

  • Shuchun Zhao

    (Stanford University)

  • Natalie J. Park

    (Stanford University)

  • Anusha Kalbasi

    (Stanford University)

  • Everett J. Moding

    (Stanford University)

  • Aaron M. Newman

    (Stanford University)

  • Ranjana H. Advani

    (Stanford University)

  • Richard T. Hoppe

    (Stanford University)

  • Maximilian Diehn

    (Stanford University)

  • Yasodha Natkunam

    (Stanford University)

  • Ash A. Alizadeh

    (Stanford University)

  • Michael Sargent Binkley

    (Stanford University)

Abstract

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and few studies have comprehensively investigated the immune microenvironment and rare lymphocyte-predominant (LP) cells. Here we develop a NLPHL specific lymphocyte-predominant ecotype (LPE) model to identify 34 distinct cell states across 14 cell types that co-occur within 3 LPEs for 171 cases. LPE1 and LPE2 were characterized by immunosuppressive microenvironments with high expression of B2M on LP cells, CD8 T-cell exhaustion, immune checkpoint genes expressed by follicular T-cells, and an improved freedom from progression compared to LPE3 in training (n = 109, with 65% LPE1/2) and validation cohorts (n = 62, with 61% LPE1/2). We validate the co-occurrence and co-localization of cell states using spatial transcriptomics. Protein expression of HLA-I and HLA-II on LP cells and SSTR2 on dendritic cells was predictive of LPE1 (C-statistic=0.69), LPE2 (C-statistic=0.79), and LPE3 (C-statistic=0.60). This study establishes a clinically relevant biologic categorization for NLPHL.

Suggested Citation

  • Ajay Subramanian & Shengqin Su & Jamie Flerlage & Stefan Alig & Sheren Younes & Lianna J. Marks & Chelsea Pinnix & Francisco Vega & Raphael Steiner & Priya Kumar & Heidi Mocikova & Alice Sykorova & Vi, 2025. "Distinct cell state ecosystems for nodular lymphocyte-predominant Hodgkin lymphoma," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63339-9
    DOI: 10.1038/s41467-025-63339-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-63339-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-63339-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63339-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.