2. Academic Validation
  3. Inosine is an alternative carbon source for CD8+-T-cell function under glucose restriction

Inosine is an alternative carbon source for CD8+-T-cell function under glucose restriction

  • Nat Metab. 2020 Jul;2(7):635-647. doi: 10.1038/s42255-020-0219-4.
Tingting Wang  # 1,  J N Rashida Gnanaprakasam  # 1,  Xuyong Chen 1,  Siwen Kang 1,  Xuequn Xu 1,  Hua Sun 2,  Lingling Liu 1,  Hayley Rodgers 1,  Ethan Miller 1,  Teresa A Cassel 3,  Qiushi Sun 3,  Sara Vicente-Muñoz 3,  Marc O Warmoes 3,  Penghui Lin 3,  Zayda Lizbeth Piedra-Quintero 4,  Mireia Guerau-de-Arellano 4,  Kevin A Cassady 1,  Song Guo Zheng 5,  Jun Yang 6,  Andrew N Lane 3,  Xiaotong Song 7 8,  Teresa W-M Fan 9,  Ruoning Wang 10
Affiliations

Affiliations

  • 1 Center for Childhood Cancer & Blood Diseases, Hematology/Oncology & BMT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Ohio State University, Columbus, OH, USA.
  • 2 The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
  • 3 Center for Environmental and Systems Biochemistry, Department of Toxicology and Cancer Biology, Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
  • 4 School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, College of Medicine, Wexner Medical Center, Ohio State University, Columbus, OH, USA.
  • 5 Division of Rheumatology and Immunology, Department of Internal Medicine at Ohio State University of Medicine and Wexner Medical Center, Columbus, OH, USA.
  • 6 Department of Surgery, St Jude Children's Research Hospital, Memphis, TN, USA.
  • 7 The Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA. shautong.song@icellkealex.com.
  • 8 Icell Kealex Therapeutics, Houston, TX, USA. shautong.song@icellkealex.com.
  • 9 Center for Environmental and Systems Biochemistry, Department of Toxicology and Cancer Biology, Markey Cancer Center, University of Kentucky, Lexington, KY, USA. twmfan@gmail.com.
  • 10 Center for Childhood Cancer & Blood Diseases, Hematology/Oncology & BMT, Abigail Wexner Research Institute at Nationwide Children's Hospital, Ohio State University, Columbus, OH, USA. ruoning.wang@nationwidechildrens.org.
  • # Contributed equally.
PMID: 32694789 DOI: 10.1038/s42255-020-0219-4
Abstract

T cells undergo metabolic rewiring to meet their bioenergetic, biosynthetic and redox demands following antigen stimulation. To fulfil these needs, effector T cells must adapt to fluctuations in environmental nutrient levels at sites of Infection and inflammation. Here, we show that effector T cells can utilize inosine, as an alternative substrate, to support cell growth and function in the absence of glucose in vitro. T cells metabolize inosine into hypoxanthine and phosphorylated ribose by purine nucleoside phosphorylase. We demonstrate that the ribose subunit of inosine can enter into central metabolic pathways to provide ATP and biosynthetic precursors, and that Cancer cells display diverse capacities to utilize inosine as a carbon source. Moreover, the supplementation with inosine enhances the anti-tumour efficacy of Immune Checkpoint blockade and adoptive T-cell transfer in solid tumours that are defective in metabolizing inosine, reflecting the capability of inosine to relieve tumour-imposed metabolic restrictions on T cells.

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