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TGF-β in T Cell Biology: Implications for Cancer Immunotherapy

Transforming Growth Factor beta (TGF-β) is a pleiotropic cytokine produced in large amounts within cancer microenvironments that will ultimately promote neoplastic progression, notably by suppressing the host’s T-cell immunosurveillance. This effect is mostly due to the well-known inhibitory effect...

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Detalles Bibliográficos
Autores principales: Dahmani, Amina, Delisle, Jean-Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025055/
https://www.ncbi.nlm.nih.gov/pubmed/29891791
http://dx.doi.org/10.3390/cancers10060194
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author Dahmani, Amina
Delisle, Jean-Sébastien
author_facet Dahmani, Amina
Delisle, Jean-Sébastien
author_sort Dahmani, Amina
collection PubMed
description Transforming Growth Factor beta (TGF-β) is a pleiotropic cytokine produced in large amounts within cancer microenvironments that will ultimately promote neoplastic progression, notably by suppressing the host’s T-cell immunosurveillance. This effect is mostly due to the well-known inhibitory effect of TGF-β on T cell proliferation, activation, and effector functions. Moreover, TGF-β subverts T cell immunity by favoring regulatory T-cell differentiation, further reinforcing immunosuppression within tumor microenvironments. These findings stimulated the development of many strategies to block TGF-β or its signaling pathways, either as monotherapy or in combination with other therapies, to restore anti-cancer immunity. Paradoxically, recent studies provided evidence that TGF-β can also promote differentiation of certain inflammatory populations of T cells, such as Th17, Th9, and resident-memory T cells (Trm), which have been associated with improved tumor control in several models. Here, we review current advances in our understanding of the many roles of TGF-β in T cell biology in the context of tumor immunity and discuss the possibility to manipulate TGF-β signaling to improve cancer immunotherapy.
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spelling pubmed-60250552018-07-09 TGF-β in T Cell Biology: Implications for Cancer Immunotherapy Dahmani, Amina Delisle, Jean-Sébastien Cancers (Basel) Review Transforming Growth Factor beta (TGF-β) is a pleiotropic cytokine produced in large amounts within cancer microenvironments that will ultimately promote neoplastic progression, notably by suppressing the host’s T-cell immunosurveillance. This effect is mostly due to the well-known inhibitory effect of TGF-β on T cell proliferation, activation, and effector functions. Moreover, TGF-β subverts T cell immunity by favoring regulatory T-cell differentiation, further reinforcing immunosuppression within tumor microenvironments. These findings stimulated the development of many strategies to block TGF-β or its signaling pathways, either as monotherapy or in combination with other therapies, to restore anti-cancer immunity. Paradoxically, recent studies provided evidence that TGF-β can also promote differentiation of certain inflammatory populations of T cells, such as Th17, Th9, and resident-memory T cells (Trm), which have been associated with improved tumor control in several models. Here, we review current advances in our understanding of the many roles of TGF-β in T cell biology in the context of tumor immunity and discuss the possibility to manipulate TGF-β signaling to improve cancer immunotherapy. MDPI 2018-06-11 /pmc/articles/PMC6025055/ /pubmed/29891791 http://dx.doi.org/10.3390/cancers10060194 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Dahmani, Amina
Delisle, Jean-Sébastien
TGF-β in T Cell Biology: Implications for Cancer Immunotherapy
title TGF-β in T Cell Biology: Implications for Cancer Immunotherapy
title_full TGF-β in T Cell Biology: Implications for Cancer Immunotherapy
title_fullStr TGF-β in T Cell Biology: Implications for Cancer Immunotherapy
title_full_unstemmed TGF-β in T Cell Biology: Implications for Cancer Immunotherapy
title_short TGF-β in T Cell Biology: Implications for Cancer Immunotherapy
title_sort tgf-β in t cell biology: implications for cancer immunotherapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025055/
https://www.ncbi.nlm.nih.gov/pubmed/29891791
http://dx.doi.org/10.3390/cancers10060194
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