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

Abstract 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...

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Autores principales:	Aleksandra E. Kmieciak, Liam V. Brown, Mark C. Coles, Jonathan Wagg, Alex Phipps, Eamonn A. Gaffney
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe7cfd469db94e7c966dffd618e7752f
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spelling	oai:doaj.org-article:fe7cfd469db94e7c966dffd618e7752f2021-12-02T16:27:44ZPredicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients10.1038/s41598-021-95225-x2045-2322https://doaj.org/article/fe7cfd469db94e7c966dffd618e7752f2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95225-xhttps://doaj.org/toc/2045-2322Abstract 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.Aleksandra E. KmieciakLiam V. BrownMark C. ColesJonathan WaggAlex PhippsEamonn A. GaffneyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Aleksandra E. Kmieciak Liam V. Brown Mark C. Coles Jonathan Wagg Alex Phipps Eamonn A. Gaffney Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients
description	Abstract 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.
format	article
author	Aleksandra E. Kmieciak Liam V. Brown Mark C. Coles Jonathan Wagg Alex Phipps Eamonn A. Gaffney
author_facet	Aleksandra E. Kmieciak Liam V. Brown Mark C. Coles Jonathan Wagg Alex Phipps Eamonn A. Gaffney
author_sort	Aleksandra E. Kmieciak
title	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_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_sort	predicted limited redistribution of t cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fe7cfd469db94e7c966dffd618e7752f
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Predicted limited redistribution of T cells to secondary lymphoid tissue correlates with increased risk of haematological malignancies in asplenic patients

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