HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: implications for immune escape in vivo.
Standard
HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: implications for immune escape in vivo. / Wischhusen, Jörg; Friese, Manuel A.; Mittelbronn, Michel; Meyermann, Richard; Weller, Michael.
In: J NEUROPATH EXP NEUR, Vol. 64, No. 6, 6, 2005, p. 523-528.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - HLA-E protects glioma cells from NKG2D-mediated immune responses in vitro: implications for immune escape in vivo.
AU - Wischhusen, Jörg
AU - Friese, Manuel A.
AU - Mittelbronn, Michel
AU - Meyermann, Richard
AU - Weller, Michael
PY - 2005
Y1 - 2005
N2 - The nonclassical MHC class I molecule HLA-E is the only known ligand for CD94/NKG2A and CD94/NKG2C expressed on NK and CD8+ alphabeta and gammadelta T cells. HLA-E may transmit either activating signals via CD94/NKG2C or inhibitory signals mediated by CD94/NKG2A. Here we show that HLA-E is expressed at mRNA and protein level in human long-term glioma cell lines, primary ex vivo polyclonal glioblastoma cell cultures and surgical glioblastoma specimens. Furthermore, immunohistochemistry revealed an enhanced in vivo expression of HLA-E in gliomas of lower grades and a massive overexpression in grade IV glioblastomas compared with normal CNS tissue. An immune-inhibitory effect of HLA-E on tumor-specific CTL has already been described. We show that siRNA-mediated silencing of HLA-E or blocking of CD94/NKG2A enables NKG2D-mediated lysis of 51Cr-labeled tumor cells by NK cells. Thus, our study provides the first evidence that expression and interaction of HLA-E on cancer cells with CD94/NKG2A expressed on lymphocytes compromises innate anti-tumor immune responses.
AB - The nonclassical MHC class I molecule HLA-E is the only known ligand for CD94/NKG2A and CD94/NKG2C expressed on NK and CD8+ alphabeta and gammadelta T cells. HLA-E may transmit either activating signals via CD94/NKG2C or inhibitory signals mediated by CD94/NKG2A. Here we show that HLA-E is expressed at mRNA and protein level in human long-term glioma cell lines, primary ex vivo polyclonal glioblastoma cell cultures and surgical glioblastoma specimens. Furthermore, immunohistochemistry revealed an enhanced in vivo expression of HLA-E in gliomas of lower grades and a massive overexpression in grade IV glioblastomas compared with normal CNS tissue. An immune-inhibitory effect of HLA-E on tumor-specific CTL has already been described. We show that siRNA-mediated silencing of HLA-E or blocking of CD94/NKG2A enables NKG2D-mediated lysis of 51Cr-labeled tumor cells by NK cells. Thus, our study provides the first evidence that expression and interaction of HLA-E on cancer cells with CD94/NKG2A expressed on lymphocytes compromises innate anti-tumor immune responses.
M3 - SCORING: Zeitschriftenaufsatz
VL - 64
SP - 523
EP - 528
JO - J NEUROPATH EXP NEUR
JF - J NEUROPATH EXP NEUR
SN - 0022-3069
IS - 6
M1 - 6
ER -
