2. Academic Validation
  3. Vitamin B6 preserves the stemness-like phenotypes and antitumor ability of CD8+ T cells

Vitamin B6 preserves the stemness-like phenotypes and antitumor ability of CD8+ T cells

  • Dev Cell. 2025 Nov 27:S1534-5807(25)00691-4. doi: 10.1016/j.devcel.2025.10.017.
Jun Wu 1,  Gen Li 2,  Jiawen Zhou 2,  Xuan Sun 2,  Haoyu Wang 3,  Haipeng Gong 3,  Peng Jiang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Oncology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China; School of Pharmaceutical Sciences, The First Affiliated Hospital, State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, Fujian 361102, China; Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong 518057, China.
  • 2 State Key Laboratory of Molecular Oncology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 3 MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 4 State Key Laboratory of Molecular Oncology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: [email protected].
PMID: 41314217 DOI: 10.1016/j.devcel.2025.10.017
Abstract

Tumor-infiltrating lymphocytes are usually dysfunctional but demonstrate stem cell-like behavior through unclear mechanisms. Here, we report that administration of vitamin B6 or its active form, pyridoxal phosphate (PLP), endows mouse and human CD8+ T cells with improved persistence, stemness-like phenotypes, and tumor clearance capabilities. Lowering PLP by pyridoxal kinase (PDXK) heterozygosity results in reduced T cell stemness-like properties and increased exhaustion phenotypes in tumors. Mechanistically, PLP preserves T cell function by directly binding to and inhibiting p70S6 kinase (p70S6K). Through limiting p70S6K-mediated BTB domain and CNC homolog 2 (BACH2) phosphorylation, PLP increases nuclear retention and functional activation of BACH2, promoting stemness gene expression while dampening exhaustion gene expression. In preclinical tumor models, PLP treatment improves the efficacy of anti-programmed death receptor 1 (PD-1) antibody therapy. Thus, our study reveals a pathway that preserves T cell functional stemness-like phenotypes to drive the acquisition of antitumor immunity, highlighting the clinical potential of vitamin B6/PLP-enhanced T cell function strategies in Cancer Immunotherapy.

Keywords

T cell differentiation; antitumor immunity; metabolite signaling; p70S6K; vitamin B6.

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