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

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.

Treatment of multiple myeloma: What is the impact on T-cell function?

“… 15 Metabolic activation was more pronounced in T cells with upregulated glycolysis and fatty acid oxidation during engraftment after ASCT. 22 ASCT also alters the molecular signatures of T cells and downregulates expression of the co-stimulatory receptors CD27 and CD28 and upregulates expression of immune checkpoints, programmed cell death protein 1 (PD-1), lymphocyte-activation gene 3 (LAG-3), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT). 23 However, T-cell exhaustion and senescence characterize the immune impairment and relapse after ASCT.…”

Natural Killer Cells Are Key Host Immune Effector Cells Affecting Survival in Autologous Peripheral Blood Hematopoietic Stem Cell Transplantation

“…Richter et al evaluated the metabolic activity of engrafted NK cells post-APBHSCT [ 59 ]. In this study, engrafted NK cells showed high expression of hexokinase 2 (HK2), the rate-limiting enzyme of glycolysis.…”