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

CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4(+) effector memory T cells (T(EMs)) in humans with unwanted serious adverse effects. It is well known that distinct metabolic programs determine the fate and responses of...

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Autores principales: 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, Webb, Steven D., Djouhri, Laiche, Ball, Christina, Stebbings, Richard, Sathish, Jean G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634261/
https://www.ncbi.nlm.nih.gov/pubmed/31009338
http://dx.doi.org/10.1089/mab.2018.0042
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author 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
Webb, Steven D.
Djouhri, Laiche
Ball, Christina
Stebbings, Richard
Sathish, Jean G.
author_facet 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
Webb, Steven D.
Djouhri, Laiche
Ball, Christina
Stebbings, Richard
Sathish, Jean G.
author_sort Thaventhiran, Thilipan
collection PubMed
description CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4(+) effector memory T cells (T(EMs)) 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(+) T(EMs) 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.
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spelling pubmed-66342612019-07-16 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 Webb, Steven D. Djouhri, Laiche Ball, Christina Stebbings, Richard Sathish, Jean G. Monoclon Antib Immunodiagn Immunother Article CD28 superagonist (CD28SA), a therapeutic immunomodulatory monoclonal antibody triggered rapid and exaggerated activation of CD4(+) effector memory T cells (T(EMs)) 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(+) T(EMs) 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. Mary Ann Liebert, Inc., publishers 2019-04-01 2019-04-22 /pmc/articles/PMC6634261/ /pubmed/31009338 http://dx.doi.org/10.1089/mab.2018.0042 Text en © Thilipan Thaventhiran et al. 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
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
Webb, Steven D.
Djouhri, Laiche
Ball, Christina
Stebbings, Richard
Sathish, Jean G.
CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program
title CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program
title_full CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program
title_fullStr CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program
title_full_unstemmed CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program
title_short CD28 Superagonistic Activation of T Cells Induces a Tumor Cell-Like Metabolic Program
title_sort cd28 superagonistic activation of t cells induces a tumor cell-like metabolic program
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634261/
https://www.ncbi.nlm.nih.gov/pubmed/31009338
http://dx.doi.org/10.1089/mab.2018.0042
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