Associations Between Myeloid-Derived Suppressor Cells, TIM-3+ T Cells, and Clinical Factors During the Post-transplant Neutropenia Period in Patients With Multiple Myeloma

TL;DR

This study explores how immune cells like MDSCs and T cells interact after a stem cell transplant in multiple myeloma patients and how these interactions relate to recovery and treatment.

Contribution

The study identifies associations between MDSCs, TIM-3+ T cells, and post-transplant clinical factors in multiple myeloma patients.

Findings

TIM-3+ CD4+ and CD8+ T cell counts were negatively associated with monocytic MDSCs at engraftment.

PMN-MDSC counts were lower in patients treated with carbapenems compared to cefepime.

Short-term G-CSF administration increased monocytic MDSCs.

Abstract

Introduction: The objective of our study was to assess relationships between circulating myeloid-derived suppressor cell (MDSC) populations and T cell subsets, up-regulating PD-1 and TIM-3, as well as their intended association with several post-transplant clinical factors.

Methods: Forty-five patients with multiple myeloma (MM) were enrolled in the study. Circulating Lin-HLA-DR-CD33+CD66b+ polymorphonuclear (PMN) MDSCs, CD14+HLA-DRlow/- monocytic (M) MDSCs, PD-1+/TIM-3+ CD4+ and CD8+ T cells were assessed with flow cytometry at the engraftment and following six post-transplant months. The frequencies of patients with common post-transplant complications, antibacterial treatment, and granulocyte colony-stimulating factor (G-CSF) administration during the neutropenia period were investigated.

Results: TIM-3+ CD4+ and CD8+ T cell counts were negatively associated with M-MDSCs at the engraftment. Both PD-1+/TIM-3+ T cells and MDSCs at the engraftment did not differ between the patients with or without febrile episodes, oral mucositis, and enteropathy during the neutropenia period. Relative counts of PMN-MDSCs were significantly lower in MM patients who received carbapenems compared to those treated with cefepime. Short-term G-CSF administration was associated with an increase in M-MDSCs.

Conclusion: Following autologous hematopoietic stem cell transplantation (HSCT), cellular interactions and the possible impact of therapeutic interventions on the immune recovery have not been fully investigated and may be of interest as predictive biomarkers and targets for novel therapies.

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