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

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, Emma Lin, Linsey Gong, Qiyu Gong, Mehdi Borji, Phillip D. Michaels, Jacob P. Laubach, Geraldine Pinkus, Gad Getz, Catherine J. Wu (), Fei Chen () and Caron Jacobson ()
Additional contact information
Katie Maurer: Dana-Farber Cancer Institute
Jackson A. Weir: Broad Institute of MIT and Harvard
Adi Nagler: Dana-Farber Cancer Institute
Nicholas J. Haradhvala: Broad Institute of MIT and Harvard
Hariharan Bharadwaj: Brigham and Women’s Hospital
Jacob Shapiro: Broad Institute of MIT and Harvard
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
Geraldine Pinkus: Brigham and Women’s Hospital
Gad Getz: Broad Institute of MIT and Harvard
Catherine J. Wu: Dana-Farber Cancer Institute
Fei Chen: Broad Institute of MIT and Harvard
Caron Jacobson: Dana-Farber Cancer Institute

Nature Communications, 2025, vol. 16, issue 1, 1-9

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62709-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62709-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62709-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().