PMID- 29967607
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Glioblastoma Stem-Like Cells Are More Susceptible Than Differentiated Cells to 
      Natural Killer Cell Lysis Mediated Through Killer Immunoglobulin-Like 
      Receptors-Human Leukocyte Antigen Ligand Mismatch and Activation Receptor-Ligand 
      Interactions.
PG  - 1345
LID - 10.3389/fimmu.2018.01345 [doi]
LID - 1345
AB  - Glioblastoma (GBM) is the most aggressive brain malignancy in adults, where 
      survival is approximately 14.6 months. Novel therapies are urgently needed and 
      immunotherapy has hailed a new dawn for treatment of solid tumors. Natural killer 
      (NK) cells may be amenable therapeutic effectors against heterogeneous GBM, since 
      they also do not require co-stimulation and antigen specificity. However, it is 
      unclear how culture media routinely used in pre-clinical studies affect GBM cell 
      responses to NK-mediated cytotoxicity. We hypothesized that the culture medium 
      would affect GBM cell phenotype, proliferation, and responses to NK cytotoxicity. 
      We investigated in paired analyses n = 6 patient-derived primary GBM cells 
      propagated in stem cell or serum-containing medium for morphology, proliferation, 
      as well as susceptibility to NK cytolysis and related this to expression of 
      surface and intracellular lineage markers, as well as ligands for NK cell 
      activating and inhibitory receptors. We genotyped the GBM cells for human 
      leukocyte antigen (HLA) as well as the killer immunoglobulin-like receptors (KIR) 
      of the n = 6 allogeneic NK cells used as effector cells. Culture in 
      serum-containing medium induced a switch in GBM cell morphology from suspension 
      neuropsheres to adherent epithelial-mesenchymal-like phenotypes, which was 
      partially reversible. The differentiated cells diminished expression of nestin, 
      CD133 (prominin-1), and A2B5 putative glioma stem-cell markers, attenuated 
      growth, diminished expression of ligands for activating NK cell receptors, while 
      upregulating class I HLA ligands for NK cell inhibitory receptors. When 
      maintained in serum-containing medium, fewer GBM cells expressed intercellular 
      cell adhesion molecule-1 (ICAM-1) and were less susceptible to lysis by NK cells 
      expressing alpha(L)beta(2) integrin receptor (LFA-1), mediated through combination of 
      inhibitory KIR-HLA ligand mismatch and diminished activation receptor-ligand 
      interactions compared to cells maintained in stem cell media. We conclude that 
      development of preclinical immunotherapy strategies against GBM should not use 
      cells propagated in serum-containing media to avoid misinterpretation of 
      potential therapeutic responses.
FAU - Haspels, Heleen Neeltje
AU  - Haspels HN
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
FAU - Rahman, Mohummad Aminur
AU  - Rahman MA
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
FAU - Joseph, Justin Vareecal
AU  - Joseph JV
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
FAU - Gras Navarro, Andrea
AU  - Gras Navarro A
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
FAU - Chekenya, Martha
AU  - Chekenya M
AD  - Department of Biomedicine, University of Bergen, Bergen, Norway.
LA  - eng
PT  - Journal Article
DEP - 20180618
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC6015895
OTO - NOTNLM
OT  - KIR-HLA interactions
OT  - NK-cells
OT  - cancer stem-like cells
OT  - differentiation
OT  - glioblastoma
OT  - killer immunoglobulin-like receptors-human leukocyte antigen ligand mismatch
OT  - natural killer cells
EDAT- 2018/07/04 06:00
MHDA- 2018/07/04 06:01
PMCR- 2018/01/01
CRDT- 2018/07/04 06:00
PHST- 2018/03/02 00:00 [received]
PHST- 2018/05/30 00:00 [accepted]
PHST- 2018/07/04 06:00 [entrez]
PHST- 2018/07/04 06:00 [pubmed]
PHST- 2018/07/04 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.01345 [doi]
PST - epublish
SO  - Front Immunol. 2018 Jun 18;9:1345. doi: 10.3389/fimmu.2018.01345. eCollection 
      2018.