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Nicotinamide Metabolism Constrains Memory CD8+ T Cell Formation Through a Putative HS1BP3-SIRT1-FOXO3-BCL6 Axis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Nicotinamide Metabolism Constrains Memory CD8+ T Cell Formation Through a Putative HS1BP3-SIRT1-FOXO3-BCL6 Axis.
Συγγραφείς: Wang S; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Fan X; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Huang Y; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Yao C; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Fan J; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Ping Y; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Zhao X; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Li C; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.; Zhongyuan Cell Therapy and Immunotherapy Laboratory, Henan Academy of Innovations in Medical Science, Zhengzhou, China., Shen C; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Shan J; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Liu J; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Wang S; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China., Zhang Z; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China., Zhang Y; Biotherapy Center and Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.; Zhongyuan Cell Therapy and Immunotherapy Laboratory, Henan Academy of Innovations in Medical Science, Zhengzhou, China.; School of Life Sciences, Zhengzhou University, Zhengzhou, Henan, China.; School of Public Health, Zhengzhou University, Zhengzhou, Henan, China.; State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer, Tianjian Laboratory of Advanced Biomedical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Πηγή: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2026 Oct; Vol. 13 (57), pp. e77284. Date of Electronic Publication: 2026 Aug 21.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE
Imprint Name(s): Original Publication: Weinheim : WILEY-VCH, [2014]-
Ιατρικοί όροι (MeSH): Niacinamide*/metabolism , CD8-Positive T-Lymphocytes*/metabolism , CD8-Positive T-Lymphocytes*/immunology , Sirtuin 1*/metabolism , Sirtuin 1*/genetics , Forkhead Box Protein O3*/metabolism , Forkhead Box Protein O3*/genetics , Proto-Oncogene Proteins c-bcl-6*/metabolism , Proto-Oncogene Proteins c-bcl-6*/genetics , Immunologic Memory*/immunology, Animals ; Mice ; Signal Transduction ; Metabolic Reprogramming
Περίληψη: Memory T cells exhibit long-term persistence, a defining feature that underpins durable clinical responses to adoptive immunotherapies. The mechanisms that integrate metabolic cues with transcriptional control of memory fate remain undetermined. Here, we identify HS1-binding protein 3 (HS1BP3) is preferentially expressed in memory CD8+ T cells. HS1BP3 deficiency reduced memory-associated gene expression in CD8+ OT-1 T cells following Listeria monocytogenes-ovalbumin infection and impaired antitumor responses. Loss of HS1BP3 induces metabolic reprogramming characterized by reduced oxidative phosphorylation (OXPHOS) and altered nicotinamide metabolism, accompanied by increased NAD+ and nicotinamide metabolite 1-methylnicotinamide (MNAM) abundance. HS1BP3 interacted with Sirtuin 1 (SIRT1), and its deficiency is associated with increased SIRT1 activity, enhanced Forkhead box O3 (FOXO3) signaling, and reduced expression of memory-associated transcription factor B cell lymphoma 6 (BCL6). Moreover, accumulation of MNAM impairs the antitumor activity of CD8+ T cells. Importantly, elevated levels of HS1BP3 drive chimeric antigen receptor (CAR) -T cells towards a memory phenotype and improve tumor control. Collectively, our findings identify HS1BP3 as a regulator of CD8+ T cell memory and indicate that its effects are associated with alterations in nicotinamide metabolism and the SIRT1-FOXO3-BCL6 signaling axis. These observations support the therapeutic potential of HS1BP3-engineered CAR-T cells across solid tumors.
(© 2026 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
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Grant Information: 2025ZD0552500 Noncommunicable Chronic Diseases-National Science and Technology Major Project; 2022YFE0141000 Intergovernmental International Science and Technology Innovation Cooperation Project; 82403844 National Natural Science Foundation of China; 262102311020 Medical Science and Technology Project of Henan Province; YQRC2023015 Health science and Technology Innovation Outstanding Young Talents Training Project; HNCRD202432 Henan Province Special Program for Clinical Research-Oriented Physicians
Contributed Indexing: Keywords: CD8+ T cell; antitumor response; memory; nicotinamide metabolism
Substance Nomenclature: 25X51I8RD4 (Niacinamide)
EC 3.5.1.- (Sirtuin 1)
0 (Forkhead Box Protein O3)
EC 3.5.1.- (Sirt1 protein, mouse)
0 (Proto-Oncogene Proteins c-bcl-6)
0 (FoxO3 protein, mouse)
Entry Date(s): Date Created: 20260821 Date Completed: 20261015 Latest Revision: 20261015
Update Code: 20261015
PubMed Central ID: PMC13495949
DOI: 10.1002/advs.77284
PMID: 42627264
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2198-3844
DOI:10.1002/advs.77284