PMID- 19234348
OWN - NLM
STAT- MEDLINE
DCOM- 20090611
LR  - 20090527
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 50
IP  - 6
DP  - 2009 Jun
TI  - Evidence for natural killer cell-mediated protection from metastasis formation in 
      uveal melanoma patients.
PG  - 2888-95
LID - 10.1167/iovs.08-2733 [doi]
AB  - PURPOSE: In uveal melanoma, low human leukocyte antigen (HLA) class I expression 
      on primary tumors is associated with a decreased risk of metastasis. 
      Consequently, it has been suggested that natural killer (NK) cells, which detect 
      decreased expression of HLA class I, are involved in the immune control of 
      metastases. In this study, three novel lines of evidence were identified that 
      support a role for NK cells. METHODS: Uveal melanoma cell lines were used to 
      determine the expression of NK cell receptor ligands (MICA, MICB, ULBP1-3, CD112, 
      CD155, and HLA class I) and to examine sensitivity to lysis by human NK cell 
      lines. Because interactions between polymorphic killer immunoglobulin receptors 
      (KIRs) and HLA regulate NK cell function, KIR and HLA genotyping was performed on 
      154 patients with uveal melanoma and 222 healthy control subjects. RESULTS: 
      First, all 11 uveal melanoma cell lines tested expressed ligands for activating 
      as well as inhibitory NK cell receptors. Second, such cell lines were lysed 
      efficiently by human NK cells in vitro. Finally, the HLA-C genotype was related 
      to the risk of metastasis-related death in patients with uveal melanoma: The 
      patients carrying HLA-C alleles encoding ligands for KIR2DL1 and KIR2DL2/3 (HLA-C 
      group 1/group 2 heterozygous patients), both inhibitory NK receptors, had a 
      longer metastasis-free survival than did those carrying HLA-C ligands for either 
      KIR2DL1 (HLA-C group 2 homozygotes) or KIR2DL2/3 (HLA-C group 1 homozygotes). 
      CONCLUSIONS: Together, the data support a role for NK cells in the prevention of 
      uveal melanoma metastases.
FAU - Maat, Willem
AU  - Maat W
AD  - Department of Ophthalmology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - van der Slik, Arno R
AU  - van der Slik AR
FAU - Verhoeven, Dirk H J
AU  - Verhoeven DH
FAU - Alizadeh, Behrooz Z
AU  - Alizadeh BZ
FAU - Ly, Long V
AU  - Ly LV
FAU - Verduijn, Willem
AU  - Verduijn W
FAU - Luyten, Gregorius P M
AU  - Luyten GP
FAU - Mulder, Arend
AU  - Mulder A
FAU - van Hall, Thorbald
AU  - van Hall T
FAU - Koning, Frits
AU  - Koning F
FAU - Jager, Martine J
AU  - Jager MJ
FAU - van Bergen, Jeroen
AU  - van Bergen J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090221
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (HLA-C Antigens)
RN  - 0 (KIR2DL1 protein, human)
RN  - 0 (KIR2DL2 protein, human)
RN  - 0 (KIR2DL3 protein, human)
RN  - 0 (Ligands)
RN  - 0 (Receptors, KIR2DL1)
RN  - 0 (Receptors, KIR2DL2)
RN  - 0 (Receptors, KIR2DL3)
RN  - 0 (Receptors, Natural Killer Cell)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Flow Cytometry
MH  - Genotype
MH  - HLA-C Antigens/genetics
MH  - Humans
MH  - Killer Cells, Natural/*physiology
MH  - Ligands
MH  - Liver Neoplasms/genetics/immunology/*prevention & control/secondary
MH  - Lymphocyte Activation
MH  - Male
MH  - Melanoma/genetics/immunology/*prevention & control/secondary
MH  - Middle Aged
MH  - Polymerase Chain Reaction
MH  - Receptors, KIR2DL1/genetics
MH  - Receptors, KIR2DL2/genetics
MH  - Receptors, KIR2DL3/genetics
MH  - Receptors, Natural Killer Cell/metabolism
MH  - Tumor Cells, Cultured
MH  - Uveal Neoplasms/genetics/immunology/pathology/*prevention & control
EDAT- 2009/02/24 09:00
MHDA- 2009/06/12 09:00
CRDT- 2009/02/24 09:00
PHST- 2009/02/24 09:00 [entrez]
PHST- 2009/02/24 09:00 [pubmed]
PHST- 2009/06/12 09:00 [medline]
AID - iovs.08-2733 [pii]
AID - 10.1167/iovs.08-2733 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2009 Jun;50(6):2888-95. doi: 10.1167/iovs.08-2733. 
      Epub 2009 Feb 21.