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

Thaventhiran, T, Wong, W, Alghanem, AF, Alhumeed, N, Aljasir, MA, Ramsey, S, Sethu, S, Yeang, HXA, Chadwick, AE, Cross, M, Webb, SD, Djouhri, L, Ball, C, Stebbings, R and Sathish, JG (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. ISSN 2167-9436

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Open Access URL: https://doi.org/10.1089/mab.2018.0042 (Published version)

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: CD28 superagonist; CD4 effector memory T cells; glycolysis; lipogenesis; oxidative phosphorylation
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Applied Mathematics
Publisher: Mary Ann Liebert
Related URLs:
Date Deposited: 14 May 2019 09:34
Last Modified: 14 May 2019 09:35
DOI or Identification number: 10.1089/mab.2018.0042
URI: http://researchonline.ljmu.ac.uk/id/eprint/10682

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