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



Thaventhiran, Thilipan, Wong, Wai, Alghanem, Ahmad F, Alhumeed, Naif ORCID: 0000-0001-5221-3073, Aljasir, Mohammad A, Ramsey, Simeon, Sethu, Swaminathan ORCID: 0000-0001-9210-2554, Yeang, Han Xian Aw, Chadwick, Amy E ORCID: 0000-0002-7399-8655, Cross, Michael ORCID: 0000-0002-5533-1232
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). pp. 60-69.

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Abstract

CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4<sup>+</sup> effector memory T cells (T<sub>EMs</sub>) 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<sup>+</sup> T<sub>EMs</sub> 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: 14 Mar 2024 18:17
DOI: 10.1089/mab.2018.0042
Open Access URL: https://www.liebertpub.com/doi/10.1089/mab.2018.00...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3038882