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Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients

The spleen, a secondary lymphoid tissue (SLT), has an important role in generation of adaptive immune responses. Although splenectomy remains a common procedure, recent studies reported poor prognosis and increased risk of haematological malignancies in asplenic patients. The high baseline trafficki...

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Autores principales: Kmieciak, Aleksandra E., Brown, Liam V., Coles, Mark C., Wagg, Jonathan, Phipps, Alex, Gaffney, Eamonn A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360980/
https://www.ncbi.nlm.nih.gov/pubmed/34385480
http://dx.doi.org/10.1038/s41598-021-95225-x
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author Kmieciak, Aleksandra E.
Brown, Liam V.
Coles, Mark C.
Wagg, Jonathan
Phipps, Alex
Gaffney, Eamonn A.
author_facet Kmieciak, Aleksandra E.
Brown, Liam V.
Coles, Mark C.
Wagg, Jonathan
Phipps, Alex
Gaffney, Eamonn A.
author_sort Kmieciak, Aleksandra E.
collection PubMed
description The spleen, a secondary lymphoid tissue (SLT), has an important role in generation of adaptive immune responses. Although splenectomy remains a common procedure, recent studies reported poor prognosis and increased risk of haematological malignancies in asplenic patients. The high baseline trafficking of T lymphocytes to splenic tissue suggests splenectomy may lead to loss of blood-borne malignant immunosurveillance that is not compensated for by the remaining SLT. To date, no quantitative analysis of the impact of splenectomy on the human T cell trafficking dynamics and tissue localisation has been reported. We developed a quantitative computational model that describes organ distribution and trafficking of human lymphocytes to explore the likely impact of splenectomy on immune cell distributions. In silico splenectomy resulted in an average reduction of T cell numbers in SLT by 35% (95%CI 0.12–0.97) and a comparatively lower, 9% (95%CI 0.17–1.43), mean decrease of T cell concentration in SLT. These results suggest that the surveillance capacity of the remaining SLT insufficiently compensates for the absence of the spleen. This may, in part, explain haematological malignancy risk in asplenic patients and raises the question of whether splenectomy has a clinically meaningful impact on patient responses to immunotherapy.
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spelling pubmed-83609802021-08-17 Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients Kmieciak, Aleksandra E. Brown, Liam V. Coles, Mark C. Wagg, Jonathan Phipps, Alex Gaffney, Eamonn A. Sci Rep Article The spleen, a secondary lymphoid tissue (SLT), has an important role in generation of adaptive immune responses. Although splenectomy remains a common procedure, recent studies reported poor prognosis and increased risk of haematological malignancies in asplenic patients. The high baseline trafficking of T lymphocytes to splenic tissue suggests splenectomy may lead to loss of blood-borne malignant immunosurveillance that is not compensated for by the remaining SLT. To date, no quantitative analysis of the impact of splenectomy on the human T cell trafficking dynamics and tissue localisation has been reported. We developed a quantitative computational model that describes organ distribution and trafficking of human lymphocytes to explore the likely impact of splenectomy on immune cell distributions. In silico splenectomy resulted in an average reduction of T cell numbers in SLT by 35% (95%CI 0.12–0.97) and a comparatively lower, 9% (95%CI 0.17–1.43), mean decrease of T cell concentration in SLT. These results suggest that the surveillance capacity of the remaining SLT insufficiently compensates for the absence of the spleen. This may, in part, explain haematological malignancy risk in asplenic patients and raises the question of whether splenectomy has a clinically meaningful impact on patient responses to immunotherapy. Nature Publishing Group UK 2021-08-12 /pmc/articles/PMC8360980/ /pubmed/34385480 http://dx.doi.org/10.1038/s41598-021-95225-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kmieciak, Aleksandra E.
Brown, Liam V.
Coles, Mark C.
Wagg, Jonathan
Phipps, Alex
Gaffney, Eamonn A.
Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients
title Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients
title_full Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients
title_fullStr Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients
title_full_unstemmed Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients
title_short Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients
title_sort predicted limited redistribution of t cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360980/
https://www.ncbi.nlm.nih.gov/pubmed/34385480
http://dx.doi.org/10.1038/s41598-021-95225-x
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