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Cellular Therapy

The impact of circulating suppressor cells in multiple myeloma patients on clinical outcome of DLIs

Bone Marrow Transplantation volume 50, pages 822–828 (2015)Cite this article

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Abstract

Allo-SCT followed by DLIs can establish long-term remissions in multiple myeloma (MM) patients. In many patients, however, the immunotherapeutic graft-versus-tumor (GVT) effect is moderate and not sustained, implying that immune suppression is mediated, among other factors, by regulatory T cells (Tregs) or myeloid-derived suppressor cells (MDSCs). Towards a better understanding and, eventually, manipulation of the immune-regulatory mechanisms in transplanted MM patients, we retrospectively sought a correlation between DLI outcome and circulating CD14+ MDSCs, CD14− MDSCs and Tregs in 53 MM patients before their first DLI. We found significantly elevated frequencies of highly suppressive CD14+ MDSCs, CD14− MDSCs and Tregs in pre-DLI samples from patients. Higher frequencies of Tregs, but not of MDSCs, were significantly associated with non-responsiveness to DLI. Furthermore, a lower frequency of Tregs predicted the development of chronic GVHD, which, in turn, displayed a high association with GVT. Elevated Treg frequencies before DLI were also associated with significantly shorter PFS and OS. Hence, our data reinforce the idea of active suppression of antitumor responses by Tregs in MM patients and therefore suggest that targeting patient Tregs before DLI may improve outcome of DLI.

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Acknowledgements

This work was partially funded by a grant from the University Medical Center Utrecht and the Multiple Myeloma Research Foundation. We thank CAJ van der Burght for help with the FACS sort experiments.

Author Contributions

LEF performed experiments and the analyses, interpreted the data and wrote the manuscript; MEE performed and analyzed the experiments; MWHR, MS, HD and WH collected and analyzed clinical data; NWCJD, HML and TM designed the study, supervised the experiments, analyzed and interpreted the data, wrote the manuscript; TM prepared the final draft.

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Authors and Affiliations

  1. Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands

    L E Franssen

  2. Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands

    L E Franssen, N W C J van de Donk, M E Emmelot, H M Lokhorst & T Mutis

  3. Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands

    M E Emmelot & T Mutis

  4. Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands

    M W H Roeven & N Schaap

  5. Department of Laboratory Medicine-Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands

    H Dolstra & W Hobo

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  1. L E Franssen
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Correspondence to T Mutis.

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Franssen, L., van de Donk, N., Emmelot, M. et al. The impact of circulating suppressor cells in multiple myeloma patients on clinical outcome of DLIs. Bone Marrow Transplant 50, 822–828 (2015). https://doi.org/10.1038/bmt.2015.48

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