title: The impact of circulating suppressor cells in multiple myeloma patients on clinical outcome of DLIs.
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.
authors: 1] Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands [2] Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors: L E
authors: LE
authors: Franssen
authors: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors: N W C J
authors: NW
authors: van de Donk
authors: 1] Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands [2] Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: M E
authors: ME
authors: Emmelot
authors: Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: M W H
authors: MW
authors: Roeven
authors: Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: N
authors: N
authors: Schaap
authors: Department of Laboratory Medicine-Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: H
authors: H
authors: Dolstra
authors: Department of Laboratory Medicine-Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: W
authors: W
authors: Hobo
authors: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors: H M
authors: HM
authors: Lokhorst
authors: 1] Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands [2] Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: T
authors: T
authors: Mutis
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D005260:Female; D020350:Graft vs Tumor Effect / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology / Q000628:therapy; D022423:Myeloid Cells / Q000276:immunology*; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*