TY - JOUR
T1 - WHO grade associated downregulation of MHC class I antigen-processing machinery components in human astrocytomas
T2 - Does it reflect a potential immune escape mechanism?
AU - Mehling, Matthias
AU - Simon, Perikles
AU - Mittelbronn, Michel
AU - Meyermann, Richard
AU - Ferrone, Soldano
AU - Weller, Michael
AU - Wiendl, Heinz
PY - 2007/8
Y1 - 2007/8
N2 - Defects of major histocompatibility complex (MHC) class I antigen-processing machinery (APM) components have been shown to contribute to immune escape of malignant cells. We investigated the expression of APM components in astrocytomas without detectable defects in HLA class I antigen expression and correlated it with grade of malignancy. Quantitative immunohistochemical analysis of astrocytomas revealed reduced expression of the cytosolic proteasome subunit low molecular weight protein 2 (LMP2), the endoplasmatic reticulum (ER) transporter associated with antigen processing-1 (TAP1), and the ER chaperone β2-microglobulin (β2m) in astrocytoma cells when compared to astrocytes from nonpathological brain. Among human WHO grade II-IV astrocytomas, downregulation of LMP2, TAP1 and β2m correlated with grade of malignancy. Furthermore, astrocytoma cell lines (n = 12) expressed all APM components analyzed at levels comparable to dendritic cells (DC), which were used for comparative purposes. However, upregulation of β2m after stimulation with inflammatory cytokines was significantly lower in astrocytoma cell lines than in control cells. Our results support the hypothesis that coordinated downregulation or impaired upregulation of certain HLA class I APM components may serve as a mechanism for astrocytoma cells to evade the host's immune response, even if HLA class I antigen surface expression is not altered.
AB - Defects of major histocompatibility complex (MHC) class I antigen-processing machinery (APM) components have been shown to contribute to immune escape of malignant cells. We investigated the expression of APM components in astrocytomas without detectable defects in HLA class I antigen expression and correlated it with grade of malignancy. Quantitative immunohistochemical analysis of astrocytomas revealed reduced expression of the cytosolic proteasome subunit low molecular weight protein 2 (LMP2), the endoplasmatic reticulum (ER) transporter associated with antigen processing-1 (TAP1), and the ER chaperone β2-microglobulin (β2m) in astrocytoma cells when compared to astrocytes from nonpathological brain. Among human WHO grade II-IV astrocytomas, downregulation of LMP2, TAP1 and β2m correlated with grade of malignancy. Furthermore, astrocytoma cell lines (n = 12) expressed all APM components analyzed at levels comparable to dendritic cells (DC), which were used for comparative purposes. However, upregulation of β2m after stimulation with inflammatory cytokines was significantly lower in astrocytoma cell lines than in control cells. Our results support the hypothesis that coordinated downregulation or impaired upregulation of certain HLA class I APM components may serve as a mechanism for astrocytoma cells to evade the host's immune response, even if HLA class I antigen surface expression is not altered.
KW - Antigen-processing machinery
KW - Astrocytoma
KW - Immune escape
KW - MHC
UR - http://www.scopus.com/inward/record.url?scp=34547112565&partnerID=8YFLogxK
U2 - 10.1007/s00401-007-0231-8
DO - 10.1007/s00401-007-0231-8
M3 - Article
C2 - 17541610
AN - SCOPUS:34547112565
SN - 0001-6322
VL - 114
SP - 111
EP - 119
JO - Acta Neuropathologica
JF - Acta Neuropathologica
IS - 2
ER -