The metabolic profile of reconstituting T-cells, NK-cells, and monocytes following autologous stem cell transplantation and its impact on outcome

Language
en
Document Type
Article
Issue Date
2023-07-03
Issue Year
2022
Authors
Richter, Silja
Böttcher, Martin
Völkl, Simon
Mackensen, Andreas
Ullrich, Evelyn
Jacobs, Benedikt
Mougiakakos, Dimitrios
Editor
Publisher
Springer Nature
Abstract

Previous studies indicated a role of the reconstituting immune system for disease outcome upon high-dose chemotherapy (HDCT) and autologous stem cell transplantation (auto-SCT) in multiple myeloma (MM) and lymphoma patients. Since immune cell metabolism and function are closely interconnected, we used flow-cytometry techniques to analyze key components and functions of the metabolic machinery in reconstituting immune cells upon HDCT/auto-SCT. We observed increased proliferative activity and an upregulation of the glycolytic and fatty acid oxidation (FAO) machinery in immune cells during engraftment. Metabolic activation was more pronounced in T-cells of advanced differentiation stages, in CD56bright NK-cells, and CD14++CD16+ intermediate monocytes. Next, we investigated a potential correlation between the immune cells’ metabolic profile and early progression or relapse in lymphoma patients within the first twelve months following auto-SCT. Here, persistently increased metabolic parameters correlated with a rather poor disease course. Taken together, reconstituting immune cells display an upregulated bioenergetic machinery following auto-SCT. Interestingly, a persistently enhanced metabolic immune cell phenotype correlated with reduced PFS. However, it remains to be elucidated, if the clinical data can be confirmed within a larger set of patients and if residual malignant cells not detected by conventional means possibly caused the metabolic activation.

Journal Title
Scientific Reports
Volume
12
Citation
Scientific Reports 12 (2022): 11406. <https://www.nature.com/articles/s41598-022-15136-3>