PMID- 20024547
OWN - NLM
STAT- MEDLINE
DCOM- 20100607
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 59
IP  - 6
DP  - 2010 Jun
TI  - Reduced immune effector cell NKG2D expression and increased levels of soluble 
      NKG2D ligands in multiple myeloma may not be causally linked.
PG  - 829-39
LID - 10.1007/s00262-009-0807-3 [doi]
AB  - BACKGROUND: There is limited understanding of the dysregulation of the innate 
      immune system in multiple myeloma (MM). We analysed the expression of the 
      activating receptor NKG2D on NK cells and T cells of MM patients and investigated 
      the impact of soluble versus membrane-bound NKG2D ligands on the expression of 
      NKG2D. DESIGN: NKG2D expression on NK cells and CD8+ alphabeta T cells from 
      patients with MM or monoclonal gammopathy of uncertain significance and healthy 
      controls was examined flow-cytometrically. Sera from patients and controls were 
      analysed for soluble NKG2D ligands (sNKG2D ligands). RESULTS: Significantly fewer 
      NK cells and CD8+ alphabeta T cells from patients expressed NKG2D compared to 
      healthy controls (NK cells: median 54% interquartile range (IQR) 32-68 versus 71% 
      IQR 44-82%, P = 0.017, CD8+ alphabeta T cells: median 63% IQR 52-81 versus 77% 
      IQR 71-90%, P = 0.018). The sNKG2D ligand sMICA was increased in patients [median 
      175 (IQR 87-295) pg/ml] versus controls [median 80 (IQR 32-129) pg/ml, P < 
      0.001], but levels of sMICA did not correlate with NKG2D expression on effector 
      cells. To elucidate the mechanism of NKG2D down-regulation, we incubated 
      lymphocytes from healthy donors in the presence of sNKG2D ligands or in 
      co-culture with MM cell lines. sNKG2D ligands in clinically relevant 
      concentrations did not down-regulate NKG2D expression, but co-culture of effector 
      cells with myeloma cells with high surface expression of NKG2D ligands reduced 
      NKG2D expression significantly. CONCLUSIONS: These results indicate that MM is 
      associated with a significant reduction in NKG2D expression which may be 
      contact-mediated rather than caused by soluble NKG2D ligands.
FAU - von Lilienfeld-Toal, Marie
AU  - von Lilienfeld-Toal M
AD  - Transplant Immunology Group, Level 3, St. James's Institute of Oncology, Bexley 
      Wing, St James's University Hospital, Leeds, LS9 7TF, UK. 
      m.lilienfeld.toal@uni-bonn.de
FAU - Frank, Susanne
AU  - Frank S
FAU - Leyendecker, Christiane
AU  - Leyendecker C
FAU - Feyler, Sylvia
AU  - Feyler S
FAU - Jarmin, Sarah
AU  - Jarmin S
FAU - Morgan, Ruth
AU  - Morgan R
FAU - Glasmacher, Axel
AU  - Glasmacher A
FAU - Marten, Angela
AU  - Marten A
FAU - Schmidt-Wolf, Ingo G H
AU  - Schmidt-Wolf IG
FAU - Brossart, Peter
AU  - Brossart P
FAU - Cook, Gordon
AU  - Cook G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091219
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily K)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (ULBP2 protein, human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - CD8-Positive T-Lymphocytes/immunology/*metabolism/pathology
MH  - Coculture Techniques
MH  - Cytotoxicity, Immunologic
MH  - GPI-Linked Proteins
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/blood
MH  - K562 Cells
MH  - Killer Cells, Natural/immunology/*metabolism/pathology
MH  - Middle Aged
MH  - Monoclonal Gammopathy of Undetermined 
      Significance/blood/*immunology/pathology/physiopathology
MH  - Multiple Myeloma/blood/*immunology/pathology/physiopathology
MH  - NK Cell Lectin-Like Receptor Subfamily K/*biosynthesis/genetics/immunology
MH  - Receptors, Antigen, T-Cell, alpha-beta/biosynthesis
MH  - Tumor Escape
PMC - PMC11030819
EDAT- 2009/12/22 06:00
MHDA- 2010/06/09 06:00
PMCR- 2009/12/19
CRDT- 2009/12/22 06:00
PHST- 2009/10/01 00:00 [received]
PHST- 2009/12/04 00:00 [accepted]
PHST- 2009/12/22 06:00 [entrez]
PHST- 2009/12/22 06:00 [pubmed]
PHST- 2010/06/09 06:00 [medline]
PHST- 2009/12/19 00:00 [pmc-release]
AID - 807 [pii]
AID - 10.1007/s00262-009-0807-3 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2010 Jun;59(6):829-39. doi: 10.1007/s00262-009-0807-3. 
      Epub 2009 Dec 19.