2026/01/16 by Taidou Hu, Ziang Zhu, Ying Luo +6 · 1 voice
Medicine · Immunology and Microbiology · #CAR-T cell therapy research #T-cell and B-cell Immunology #Immunotherapy and Immune Responses
paper · doi:10.1038/s41590-025-02388-0
openalex publication_date 2026/01/16 · openalex created_date 2026/01/17 · openalex updated_date 2026/07/29
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 expression in CAR T cells during manufacturing using chemical switches fine-tunes the degree of stemness and imprints greater control of solid tumors. Together, these data show that BACH2 dosage defines stemness hierarchy in CAR T cells and can be temporally and tunably controlled to optimize differentiation and antitumor efficacy.