Two-stage CD8+ CAR T-cell differentiation in patients with large B-cell lymphoma
Guoshuai Cao,
Yifei Hu,
Tony Pan,
Erting Tang,
Nicholas Asby,
Thomas Althaus,
Jun Wan,
Peter A. Riedell,
Michael R. Bishop,
Justin P. Kline and
Jun Huang ()
Additional contact information
Guoshuai Cao: University of Chicago
Yifei Hu: University of Chicago
Tony Pan: University of Chicago
Erting Tang: University of Chicago
Nicholas Asby: University of Chicago
Thomas Althaus: University of Chicago
Jun Wan: Indiana University School of Medicine
Peter A. Riedell: University of Chicago
Michael R. Bishop: University of Chicago
Justin P. Kline: University of Chicago
Jun Huang: University of Chicago
Nature Communications, 2025, vol. 16, issue 1, 1-18
Abstract:
Abstract Advancements in chimeric antigen receptor (CAR) T-cell therapy for treating diffuse large B-cell lymphoma (DLBCL) have been limited by an incomplete understanding of CAR T-cell differentiation in patients. Here, we show via single-cell, multi-modal, and longitudinal analyses, that CD8+ CAR T cells from DLBCL patients successfully treated with axicabtagene ciloleucel undergo two distinct waves of clonal expansion in vivo. The first wave is dominated by an exhausted-like effector memory phenotype during peak expansion (day 8–14). The second wave is dominated by a terminal effector phenotype during the post-peak persistence period (day 21–28). Importantly, the two waves have distinct ontogeny from the infusion product and are biologically uncoupled. Precursors of the first wave exhibit more effector-like signatures, whereas precursors of the second wave exhibit more stem-like signatures. We demonstrate that CAR T-cell expansion and persistence are mediated by clonally, phenotypically, and ontogenically distinct CAR T-cell populations that serve complementary clinical purposes.
Date: 2025
References: Add references at CitEc
Citations:
Downloads: (external link)
https://www.nature.com/articles/s41467-025-59298-w 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_s41467-025-59298-w
Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/
DOI: 10.1038/s41467-025-59298-w
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 ().