title: NK Cell Subgroups, Phenotype, and Functions After Autologous Stem Cell Transplantation.
abstract: High-dose chemotherapy with consecutive autologous stem cell transplantation (autoSCT) is a well-established treatment option for patients suffering from malignant lymphoma or multiple myeloma. Natural killer (NK) cells are an important part of the immune surveillance, and their cell number after autoSCT is predictive for progression-free and overall survival. To improve knowledge about the role of NK cells after autoSCT, we investigated different NK cell subgroups, their phenotype, and their functions in patients treated with autoSCT. Directly after leukocyte regeneration (>1000 leukocytes/μl) following autoSCT, CD56(++) NK cells were the major NK cell subset. Surprisingly, these cells showed unusually high surface expression levels of CD57 and killer Ig-like receptors (KIRs) compared to expression levels before or at later time points after autoSCT. Moreover, these NK cells strongly upregulated KIR2DL2/3/S2 and KIR3DL1, whereas KIR2DL1/S1 remained constant, indicating that this cell population arose from more immature NK cells instead of from activated mature ones. Remarkably, NK cells were already able to degranulate and produce IFN-γ and MIP-1β upon tumor interaction early after leukocyte regeneration. In conclusion, we describe an unusual upregulation of CD57 and KIRs on CD56(++) NK cells shortly after autoSCT. Importantly, these NK cells were functionally competent upon tumor interaction at this early time point.
authors.affiliation: Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Radiumhospital , Oslo , Norway ; The KG Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, University of Oslo , Oslo , Norway ; Department of Haematology and Oncology, University Hospital Erlangen , Erlangen , Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Jacobs
authors.affiliation: Department of Pediatric Stem Cell Transplantation and Immunology, Children's Hospital, Johann Wolfgang Goethe-University , Frankfurt , Germany ; LOEWE Center for Cell and Gene Therapy, Johann Wolfgang Goethe-University , Frankfurt , Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Tognarelli
authors.affiliation: Department of Haematology and Oncology, University Hospital Erlangen , Erlangen , Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Poller
authors.affiliation: Department of Pediatric Stem Cell Transplantation and Immunology, Children's Hospital, Johann Wolfgang Goethe-University , Frankfurt , Germany ; LOEWE Center for Cell and Gene Therapy, Johann Wolfgang Goethe-University , Frankfurt , Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.affiliation: Department of Haematology and Oncology, University Hospital Erlangen , Erlangen , Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mackensen
authors.affiliation: Department of Haematology and Oncology, University Hospital Erlangen , Erlangen , Germany ; Department of Pediatric Stem Cell Transplantation and Immunology, Children's Hospital, Johann Wolfgang Goethe-University , Frankfurt , Germany ; LOEWE Center for Cell and Gene Therapy, Johann Wolfgang Goethe-University , Frankfurt , Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ullrich
keywords: CD107a expression; CD57; IFN-γ production; KIR; NK cells; autologous stem cell transplantation