HLA-E contributes to an immune-inhibitory phenotype of glioblastoma stem-like cells
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HLA-E contributes to an immune-inhibitory phenotype of glioblastoma stem-like cells. / Wolpert, Fabian; Roth, Patrick; Lamszus, Katrin; Tabatabai, Ghazaleh; Weller, Michael; Eisele, Günter.
In: J NEUROIMMUNOL, Vol. 250, No. 1-2, 15.09.2012, p. 27-34.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - HLA-E contributes to an immune-inhibitory phenotype of glioblastoma stem-like cells
AU - Wolpert, Fabian
AU - Roth, Patrick
AU - Lamszus, Katrin
AU - Tabatabai, Ghazaleh
AU - Weller, Michael
AU - Eisele, Günter
N1 - Copyright © 2012 Elsevier B.V. All rights reserved.
PY - 2012/9/15
Y1 - 2012/9/15
N2 - Cancer stem cells are an attractive target for immunotherapeutic approaches to glioblastoma. However, an immune inhibitory phenotype of cells currently classified as "glioma-initiating cells" (GIC) might counteract recognition by immune effector cells. Here, we investigate the contribution of the non-classical MHC molecule HLA-E to the immunosuppressive phenotype of GIC. HLA-E is expressed in GIC lines and its expression is reduced upon differentiation of GIC in serum-containing culture conditions. Constitutive HLA-E inhibits natural killer (NK) cell-mediated lysis of GIC since small-interfering RNA-mediated HLA-E gene silencing enhances the immunogenicity of GIC. Increased GIC lysis was observed both in the CD133+ and in the CD133- compartment. Furthermore, the use of interferon-γ as a possible agent to boost an immune response against glioblastoma cells might be limited by the concurrent upregulation of HLA-E.
AB - Cancer stem cells are an attractive target for immunotherapeutic approaches to glioblastoma. However, an immune inhibitory phenotype of cells currently classified as "glioma-initiating cells" (GIC) might counteract recognition by immune effector cells. Here, we investigate the contribution of the non-classical MHC molecule HLA-E to the immunosuppressive phenotype of GIC. HLA-E is expressed in GIC lines and its expression is reduced upon differentiation of GIC in serum-containing culture conditions. Constitutive HLA-E inhibits natural killer (NK) cell-mediated lysis of GIC since small-interfering RNA-mediated HLA-E gene silencing enhances the immunogenicity of GIC. Increased GIC lysis was observed both in the CD133+ and in the CD133- compartment. Furthermore, the use of interferon-γ as a possible agent to boost an immune response against glioblastoma cells might be limited by the concurrent upregulation of HLA-E.
KW - Brain Neoplasms
KW - Cell Line, Tumor
KW - Flow Cytometry
KW - Glioblastoma
KW - Histocompatibility Antigens Class I
KW - Humans
KW - Killer Cells, Natural
KW - Neoplastic Stem Cells
KW - Phenotype
KW - Real-Time Polymerase Chain Reaction
U2 - 10.1016/j.jneuroim.2012.05.010
DO - 10.1016/j.jneuroim.2012.05.010
M3 - SCORING: Journal article
C2 - 22688424
VL - 250
SP - 27
EP - 34
JO - J NEUROIMMUNOL
JF - J NEUROIMMUNOL
SN - 0165-5728
IS - 1-2
ER -