NK Cells and PMN-MDSCs in the Graft From G-CSF Mobilized Haploidentical Donors Display Distinct Gene Expression Profiles From Those of the Non-Mobilized Counterpart

Front Immunol. 2021 Apr 27;12:657329. doi: 10.3389/fimmu.2021.657329. eCollection 2021.

Abstract

A recent approach of hematopoietic stem cell (HSC) transplantation from haploidentical donors "mobilized" with G-CSF is based on the selective depletion of αβ T and B lymphocytes from the graft. Through this approach, the patient receives both HSC and mature donor-derived effector cells (including NK cells), which exert both anti-leukemia activity and protection against infections. We previously showed that donor HSC mobilization with G-CSF results in accumulation in the graft of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), capable of inhibiting in vitro the anti-leukemia activity of allogeneic NK cells. Here, we performed a detailed gene expression analysis on NK cells and PMN-MDSCs both derived from mobilized graft. Cytotoxicity assays and real time PCR arrays were performed in NK cells. Microarray technology followed by bioinformatics analysis was used for gene expression profiling in PMN-MDSCs. Results indicate that NK cells from the graft have a lower cytolytic activity as compared to those from non-mobilized samples. Further, mobilized PMN-MDSCs displayed a peculiar transcriptional profile distinguishing them from non-mobilized ones. Differential expression of pro-proliferative and immune-modulatory genes was detected in mobilized PMN-MDSCs. These data strengthen the concept that G-CSF-mobilized PMN-MDSCs present in the graft display unique molecular characteristics, in line with the strong inhibitory effect on donor NK cells.

Keywords: NK cells; hematopoietic stem cell transplantation (HSCT); leukemia; microarray gene expression analysis; myeloid-derived suppressor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival
  • Computational Biology / methods
  • Cytotoxicity, Immunologic
  • Gene Expression Profiling / methods
  • Gene Expression Regulation
  • Graft Survival / genetics
  • Graft Survival / immunology
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Hematopoietic Stem Cell Mobilization* / methods
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Leukemia / therapy
  • Myeloid-Derived Suppressor Cells / immunology
  • Myeloid-Derived Suppressor Cells / metabolism*
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Transcriptome* / drug effects
  • Transplantation, Haploidentical

Substances

  • Granulocyte Colony-Stimulating Factor