IL-2 stimulated but not unstimulated NK cells induce selective disappearance of peripheral blood cells: concomitant results to a phase I/II study
| Autor: | Melanie Bremm, Ruth Esser, Heiko Mühl, Petra S. A. Becker, Stephan Kloess, Peter Bader, Dirk Schwabe, Jan Soerensen, Hermann Kreyenberg, Christian Seidl, Ulrike Koehl, Andrea Quaiser, Sabine Huenecke, Claudia Brehm, Thomas Klingebiel, Jakob Passweg |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Male Chemokine Adoptive cell transfer medicine.medical_treatment Cancer Treatment lcsh:Medicine NK cells Clinical immunology Immunotherapy Adoptive Pediatrics Cytotoxic T cell Bone Marrow and Stem Cell Transplantation L-Selectin lcsh:Science Child Multidisciplinary Leukemia biology Chemistry Immune cells Hematology CD56 Antigen Killer Cells Natural Cytokine Oncology Cytokines Medicine Female Immunotherapy Stem cell medicine.drug Research Article Interleukin 2 Adult Adolescent Clinical Research Design Immunology Young Adult Antigens CD medicine Humans Lectins C-Type Clinical Trials Pediatric Hematology ddc:610 Biology lcsh:R Receptors IgG Molecular biology Pediatric Oncology Immune System biology.protein Interleukin-2 lcsh:Q Ex vivo |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 11, p e27351 (2011) |
| Popis: | In an ongoing clinical phase I/II study, 16 pediatric patients suffering from high risk leukemia/tumors received highly purified donor natural killer (NK) cell immunotherapy (NK-DLI) at day (+3) +40 and +100 post haploidentical stem cell transplantation. However, literature about the influence of NK-DLI on recipient's immune system is scarce. Here we present concomitant results of a noninvasive in vivo monitoring approach of recipient's peripheral blood (PB) cells after transfer of either unstimulated (NK-DLI(unstim)) or IL-2 (1000 U/ml, 9–14 days) activated NK cells (NK-DLI(IL-2 stim)) along with their ex vivo secreted cytokine/chemokines. We performed phenotypical and functional characterizations of the NK-DLIs, detailed flow cytometric analyses of various PB cells and comprehensive cytokine/chemokine arrays before and after NK-DLI. Patients of both groups were comparable with regard to remission status, immune reconstitution, donor chimerism, KIR mismatching, stem cell and NK-DLI dose. Only after NK-DLI(IL-2 stim) was a rapid, almost complete loss of CD56(bright)CD16(dim/−) immune regulatory and CD56(dim)CD16(+) cytotoxic NK cells, monocytes, dendritic cells and eosinophils from PB circulation seen 10 min after infusion, while neutrophils significantly increased. The reduction of NK cells was due to both, a decrease in patients' own CD69(−) NCR(low)CD62L(+) NK cells as well as to a diminishing of the transferred cells from the NK-DLI(IL-2 stim) with the CD56(bright)CD16(+/−)CD69(+)NCR(high)CD62L(−) phenotype. All cell counts recovered within the next 24 h. Transfer of NK-DLI(IL-2 stim) translated into significantly increased levels of various cytokines/chemokines (i.e. IFN-γ, IL-6, MIP-1β) in patients' PB. Those remained stable for at least 1 h, presumably leading to endothelial activation, leukocyte adhesion and/or extravasation. In contrast, NK-DLI(unstim) did not cause any of the observed effects. In conclusion, we assume that the adoptive transfer of NK-DLI(IL-2 stim) under the influence of ex vivo and in vivo secreted cytokines/chemokines may promote NK cell trafficking and therefore might enhance efficacy of immunotherapy. |
| Databáze: | OpenAIRE |
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