CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program.



Thaventhiran, Thilipan, Wong, Wai, Alghanem, Ahmad F, Alhumeed, Naif, Aljasir, Mohammad A, Ramsey, Simeon, Sethu, Swaminathan, Yeang, Han Xian Aw, Chadwick, Amy E, Cross, Michael
et al (show 5 more authors) (2019) CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program. Monoclonal antibodies in immunodiagnosis and immunotherapy, 38 (2). 60 - 69.

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Abstract

CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4+ effector memory T cells (TEMs) in humans with unwanted serious adverse effects. It is well known that distinct metabolic programs determine the fate and responses of immune cells. In this study, we show that human CD4+ TEMs stimulated with CD28SA adopt a metabolic program similar to those of tumor cells with enhanced glucose utilization, lipid biosynthesis, and proliferation in hypoxic conditions. Identification of metabolic profiles underlying hyperactive T cell activation would provide a platform to test safety of immunostimulatory antibodies.

Item Type: Article
Uncontrolled Keywords: CD4-Positive T-Lymphocytes, Tumor Cells, Cultured, Humans, Neoplasms, Acetyl Coenzyme A, Protein Kinases, Glucose, Antibodies, Monoclonal, Lymphocyte Activation, Cell Proliferation, Immunologic Memory, Glycolysis, Lipogenesis, T-Lymphocytes, Regulatory, CD28 Antigens
Depositing User: Symplectic Admin
Date Deposited: 29 Apr 2019 11:04
Last Modified: 18 Jan 2020 11:10
DOI: 10.1089/mab.2018.0042
Open Access URL: https://www.liebertpub.com/doi/10.1089/mab.2018.00...
URI: http://livrepository.liverpool.ac.uk/id/eprint/3038882