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Modification of NK cell subset repartition and functions in granulocyte colony-stimulating factor-mobilized leukapheresis after expansion with IL-15

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Abstract

The ability of natural killer (NK) cells to kill tumor cells without antigen recognition makes them appealing as an adoptive immunotherapy. However, NK cells are not routinely used in the context of leukemic relapse after hematopoietic stem cell transplantation. Patients who experience relapse can be treated with donor lymphocyte infusions (DLI) based on small-cell fractions frozen at the time of transplantation. Since peripheral blood stem cells (PBSCs) are increasingly used as a stem cell source and as a source of cells for DLI, we aimed to evaluate the impact of G-SCF mobilization on NK cell phenotype, subset repartition, and functionality. Immunomagnetically isolated NK cells from healthy donor blood, donor PBSCs, and patient PBSCs were expanded for 14 days with IL-15. The expansion capacity, phenotype, and functions (cytokine secretion and cytotoxicity) of NK cell subsets based on CD56 and CD16 expression were then evaluated. Mobilized sources showed a significant decrease of CD56brightCD16+ NK cells (28 versus 74%), whereas a significant increase (64 versus 15%) of CD56brightCD16− NK cells was observed in comparison with peripheral blood. Patient-mobilized NK cells showed a significantly decreased cytotoxicity, and antibody-dependent cell cytototoxicity (ADCC) was also observed to a lesser extent in NK cells from healthy donor PBSC. G-CSF-mobilized NK cell TNF-α and IFN-γ secretion was impaired at day 0 compared to healthy donors but was progressively restored after culture. In conclusion, expansion of NK cells from G-CSF-mobilized sources may progressively improve their functionality.

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Funding

This study was supported by an Overseas Study Fellowship from the China Council, [http://www.csc.edu.cn/], no. 201308420488 and the Direction de la Recherche Clinique of the CHRU of Nancy.

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Authors and Affiliations

  1. Cell Therapy Department, University Hospital of Nancy, Vandoeuvre les Nancy, France

    Yu Xiong, Manon Mouginot, Loic Reppel, Chongsheng Qian, Jean-francois Stoltz, Danièle Bensoussan & Véronique Decot

  2. Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, China

    Yu Xiong

  3. UMR CNRS UL 7365, Lorraine University, Vandoeuvre les Nancy, France

    Loic Reppel, Jean-francois Stoltz, Danièle Bensoussan & Véronique Decot

Authors
  1. Yu Xiong
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  2. Manon Mouginot
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  3. Loic Reppel
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  4. Chongsheng Qian
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  5. Jean-francois Stoltz
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  6. Danièle Bensoussan
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  7. Véronique Decot
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Contributions

YX performed the experiments. MM performed the ADCC assay. LR and DB read and correct the paper. JFS provides advices on the paper. CQ designed the ADCC assay. VD designs the experiments and writes and submits the paper.

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Correspondence to Véronique Decot.

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The authors declare they have no conflict of interest.

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Xiong, Y., Mouginot, M., Reppel, L. et al. Modification of NK cell subset repartition and functions in granulocyte colony-stimulating factor-mobilized leukapheresis after expansion with IL-15. Immunol Res 65, 1130–1138 (2017). https://doi.org/10.1007/s12026-017-8955-6

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  • DOI: https://doi.org/10.1007/s12026-017-8955-6

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