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Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients

BACKGROUND: Although regulatory T cells (Treg) are highly enriched in human tumours compared with peripheral blood, expression of the immune-checkpoint receptors, immunosuppressive molecules and function of Treg in these two sites remains undefined. METHODS: Tumour-infiltrating lymphocytes and perip...

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Autores principales: Jie, H-B, Gildener-Leapman, N, Li, J, Srivastava, R M, Gibson, S P, Whiteside, T L, Ferris, R L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833228/
https://www.ncbi.nlm.nih.gov/pubmed/24169351
http://dx.doi.org/10.1038/bjc.2013.645
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author Jie, H-B
Gildener-Leapman, N
Li, J
Srivastava, R M
Gibson, S P
Whiteside, T L
Ferris, R L
author_facet Jie, H-B
Gildener-Leapman, N
Li, J
Srivastava, R M
Gibson, S P
Whiteside, T L
Ferris, R L
author_sort Jie, H-B
collection PubMed
description BACKGROUND: Although regulatory T cells (Treg) are highly enriched in human tumours compared with peripheral blood, expression of the immune-checkpoint receptors, immunosuppressive molecules and function of Treg in these two sites remains undefined. METHODS: Tumour-infiltrating lymphocytes and peripheral blood lymphocytes were isolated from a cohort of head and neck squamous cell carcinoma (HNSCC) patients. The immunosuppressive phenotypes and function of intratumoral Treg were compared with those of peripheral blood Treg. RESULTS: The frequency of immune-checkpoint receptor-positive cells was higher on intratumoral FOXP3(+)CD25(hi) Treg compared with circulating Treg (CTLA-4, P=0.002; TIM-3, P=0.002 and PD-1, P=0.002). Immunosuppressive effector molecules, LAP and ectonucleotidase CD39 were also upregulated on intratumoral FOXP3(+) Treg (P=0.002 and P=0.004, respectively). CTLA-4 and CD39 were co-expressed on the majority of intratumoral FOXP3(+)CD4(+) Treg, suggesting that these molecules have a key role in regulatory functions of these cells in situ. Notably, intratumoral Treg exhibited more potently immunosuppressive activity than circulating Treg. CONCLUSION: These results indicate that intratumoral Treg are more immunosuppressive than circulating Treg and CTLA-4 and CD39 expressed can be potential target molecules to inhibit suppressive activities of intratumoral Treg in situ.
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spelling pubmed-38332282014-11-12 Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients Jie, H-B Gildener-Leapman, N Li, J Srivastava, R M Gibson, S P Whiteside, T L Ferris, R L Br J Cancer Molecular Diagnostics BACKGROUND: Although regulatory T cells (Treg) are highly enriched in human tumours compared with peripheral blood, expression of the immune-checkpoint receptors, immunosuppressive molecules and function of Treg in these two sites remains undefined. METHODS: Tumour-infiltrating lymphocytes and peripheral blood lymphocytes were isolated from a cohort of head and neck squamous cell carcinoma (HNSCC) patients. The immunosuppressive phenotypes and function of intratumoral Treg were compared with those of peripheral blood Treg. RESULTS: The frequency of immune-checkpoint receptor-positive cells was higher on intratumoral FOXP3(+)CD25(hi) Treg compared with circulating Treg (CTLA-4, P=0.002; TIM-3, P=0.002 and PD-1, P=0.002). Immunosuppressive effector molecules, LAP and ectonucleotidase CD39 were also upregulated on intratumoral FOXP3(+) Treg (P=0.002 and P=0.004, respectively). CTLA-4 and CD39 were co-expressed on the majority of intratumoral FOXP3(+)CD4(+) Treg, suggesting that these molecules have a key role in regulatory functions of these cells in situ. Notably, intratumoral Treg exhibited more potently immunosuppressive activity than circulating Treg. CONCLUSION: These results indicate that intratumoral Treg are more immunosuppressive than circulating Treg and CTLA-4 and CD39 expressed can be potential target molecules to inhibit suppressive activities of intratumoral Treg in situ. Nature Publishing Group 2013-11-12 2013-10-29 /pmc/articles/PMC3833228/ /pubmed/24169351 http://dx.doi.org/10.1038/bjc.2013.645 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Molecular Diagnostics
Jie, H-B
Gildener-Leapman, N
Li, J
Srivastava, R M
Gibson, S P
Whiteside, T L
Ferris, R L
Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients
title Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients
title_full Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients
title_fullStr Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients
title_full_unstemmed Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients
title_short Intratumoral regulatory T cells upregulate immunosuppressive molecules in head and neck cancer patients
title_sort intratumoral regulatory t cells upregulate immunosuppressive molecules in head and neck cancer patients
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833228/
https://www.ncbi.nlm.nih.gov/pubmed/24169351
http://dx.doi.org/10.1038/bjc.2013.645
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