BACH2 dosage establishes the hierarchy of stemness and fine-tunes antitumor immunity in CAR T cells

Hu, Taidou; Zhu, Ziang; Luo, Ying; Wizzard, Safuwra; Hoar, Jonathan; Shinde, S; Yihunie, Kiddist; Yao, Chen; Wu, Tuoqi

doi:10.1038/s41590-025-02388-0

articleNature ImmunologyJan 16, 2026HYBRID OA

BACH2 dosage establishes the hierarchy of stemness and fine-tunes antitumor immunity in CAR T cells

THTaidou Hu ZZZiang Zhu YLYing Luo SWSafuwra Wizzard JHJonathan Hoar

The University of Texas Southwestern Medical Center · Southwestern Medical Center

PubMed

Indexed incrossrefpubmed

Abstract

Stem-like T cells promote the efficacy of immunotherapy and are heterogeneous in stemness, with long-term (LT) stem-like T cells at the apex of this hierarchy. How the stemness hierarchy is regulated in chimeric antigen receptor (CAR) T cells and how it affects antitumor function are unclear. Here we show that BACH2 dose-dependently regulates LT stem-like differentiation and antitumor immunity of CAR T cells. LT stem-like CAR T cells that appear before infusion and re-emerge after tumor clearance have superior antitumor immunity and the greatest BACH2 expression. BACH2 promotes the antitumor response of CAR T cells and the LT stem-like transcriptional program. Temporal and quantitative induction of BACH2…

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Topics & keywords

Topics

Keywords

Chimeric antigen receptor
Hierarchy
Immunotherapy
Immunity
Function (biology)
Stem cell
Antigen

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