4.7 Article

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

Journal

SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41598-021-95225-x

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Funding

  1. Engineering and Physical Sciences Research Council (EPSRC) [EP/L016044/1]

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Studies have shown that splenectomy leads to a decrease in both the number and concentration of T cells in remaining lymphoid tissue, suggesting insufficient compensation for the loss of spleen's immune surveillance function, potentially increasing the risk of haematological malignancies in patients without a spleen.
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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