ArticleLeukemia2020
Targeting NAD immunometabolism limits severe graft-versus-host disease and has potent antileukemic activity.
Article in Leukemia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 22 citations in OpenAlex.
- Nicotinamide riboside enhances adoptive T cell therapy by promoting memory differentiation and metabolic fitness.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Immunosenescence and cancer predisposition in pediatric transplant recipients: An emerging paradigm.World journal of transplantation · 2026Review
- Redox index and capacity analysis (RICA) reveals NAD biology changes in T cell responses in vitro and ex vivo.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- NADAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cytoplasmic NAD/H synthesis via NRK1 regulates inflammatory capacity and promotes survival of CD4Nature communications · 2026Article
- Sphingolipid metabolism and hematologic disorders: current understanding and future directions.Frontiers in physiology · 2026Review
- Article
- Sirtuin 2 regulates neutrophil functions through NADiScience · 2024Article
- Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics.Science immunology · 2024Article
- NADCellular & molecular immunology · 2023Article
- Tumor-intrinsic metabolic reprogramming and how it drives resistance to anti-PD-1/PD-L1 treatment.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- The NADPH oxidase NOX2 is a marker of adverse prognosis involved in chemoresistance of acute myeloid leukemias.Haematologica · 2022Article
- Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing.British journal of pharmacology · 2022Review
- After virus exposure, early bystander naïve CD8 T cell activation relies on NADFrontiers in immunology · 2022Article
- Targeting immune cell metabolism in kidney diseases.Nature reviews. Nephrology · 2021Review
- Recent Metabolic Advances for Preventing and Treating Acute and Chronic Graft Versus Host Disease.Frontiers in immunology · 2021Review
- The Key Role of NADFrontiers in immunology · 2021Review
- Immunometabolism in haematopoietic stem cell transplantation and adoptive cellular therapies.Current opinion in hematology · 2020Review
- Immunometabolic Status of COVID-19 Cancer Patients.Physiological reviews · 2020Review
- Catalytic, Transition-Metal-Free Semireduction of Propiolamide Derivatives: Scope and Mechanistic Investigation.Organic letters · 2020Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute graft-versus-host disease (aGVHD) and tumor relapse remain major complications after allogeneic hematopoietic stem cell transplantation. Alloreactive T cells and cancer cells share a similar metabolic phenotype to meet the bioenergetic demands necessary for cellular proliferation and effector functions. Nicotinamide adenine dinucleotide (NAD) is an essential co-factor in energy metabolism and is constantly replenished by nicotinamide phosphoribosyl-transferase (Nampt), the rate-limiting enzyme in the NAD salvage pathway. Here we show, that Nampt blockage strongly ameliorates aGVHD and limits leukemic expansion. Nampt was highly elevated in serum of patients with gastrointestinal GVHD and was particularly abundant in human and mouse intestinal T cells. Therapeutic application of the Nampt small-molecule inhibitor, Fk866, strongly attenuated experimental GVHD and caused NAD depletion in T-cell subsets, which displayed differential susceptibility to NAD shortage. Fk866 robustly inhibited expansion of alloreactive but not memory T cells and promoted FoxP3-mediated lineage stability in regulatory T cells. Furthermore, Fk866 strongly reduced the tumor burden in mouse leukemia and graft-versus-leukemia models. Ex vivo studies using lymphocytes from GVHD patients demonstrated potent antiproliferative properties of Fk866, suggesting potential clinical utility. Thus, targeting NAD immunometabolism represents a novel approach to selectively inhibit alloreactive T cells during aGVHD with additional antileukemic efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.