IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-62709-7.html
   My bibliography  Save this article

A clonally expanded nodal T-cell population diagnosed as T-cell lymphoma after CAR-T therapy

Author

Listed:
  • Katie Maurer

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Jackson A. Weir

    (Broad Institute of MIT and Harvard
    Harvard University)

  • Adi Nagler

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Nicholas J. Haradhvala

    (Broad Institute of MIT and Harvard)

  • Hariharan Bharadwaj

    (Brigham and Women’s Hospital)

  • Jacob Shapiro

    (Broad Institute of MIT and Harvard
    Harvard University)

  • Somkene Alakwe

    (Broad Institute of MIT and Harvard)

  • Vipin Kumar

    (Broad Institute of MIT and Harvard)

  • Brianna Waller

    (Brigham and Women’s Hospital)

  • Mikaela McDonough

    (Dana-Farber Cancer Institute)

  • Jamie Cruz

    (Dana-Farber Cancer Institute)

  • Loida Luna

    (Dana-Farber Cancer Institute)

  • Emma Lin

    (Dana-Farber Cancer Institute)

  • Linsey Gong

    (Broad Institute of MIT and Harvard)

  • Qiyu Gong

    (Broad Institute of MIT and Harvard)

  • Mehdi Borji

    (Broad Institute of MIT and Harvard)

  • Phillip D. Michaels

    (Brigham and Women’s Hospital)

  • Jacob P. Laubach

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Geraldine Pinkus

    (Brigham and Women’s Hospital)

  • Gad Getz

    (Broad Institute of MIT and Harvard)

  • Catherine J. Wu

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of MIT and Harvard)

  • Fei Chen

    (Broad Institute of MIT and Harvard)

  • Caron Jacobson

    (Dana-Farber Cancer Institute
    Harvard Medical School)

Abstract

Reports of secondary malignancies after chimeric antigen receptor (CAR)-T and possible CAR-T derived malignant transformation necessitate caution. Here we describe a patient with diffuse large B-cell lymphoma who developed new lymphadenopathy 2.5 years after CAR-T in the context of COVID-19 infection with histopathologic features consistent with T-cell lymphoma (TCL). Deep molecular interrogation with genomic sequencing and single-cell spatial transcriptomics reveals a highly proliferative clonal T-cell population co-expressing CD4 and CD8 with biallelic TCR rearrangement and no evidence of the CAR construct. The expanded clonotype displayed T follicular helper (TFH) cell transcriptomic programs and occupies immune-excluded spatial niches within the lymph node, supportive of TFH-like neoplastic T cell behavior. Remarkably, the lymphadenopathy spontaneously resolved on interval imaging. Our data underscore the need for better understanding of post-CAR-T clonal T-cell lymphoproliferative disorders to avoid unnecessary treatment and higher specificity in diagnostic methods for TCL.

Suggested Citation

  • Katie Maurer & Jackson A. Weir & Adi Nagler & Nicholas J. Haradhvala & Hariharan Bharadwaj & Jacob Shapiro & Somkene Alakwe & Vipin Kumar & Brianna Waller & Mikaela McDonough & Jamie Cruz & Loida Luna, 2025. "A clonally expanded nodal T-cell population diagnosed as T-cell lymphoma after CAR-T therapy," Nature Communications, Nature, vol. 16(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62709-7
    DOI: 10.1038/s41467-025-62709-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-62709-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-62709-7?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_s41467-025-62709-7. 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.