Human leukocyte antigen and antigen processing machinery component defects in astrocytic tumors.
OBJECTIVE
To determine the frequency of abnormalities in human leukocyte antigen (HLA) and antigen processing machinery (APM) component expression in malignant brain tumors. This information may contribute to our understanding of the immune escape mechanisms used by malignant brain tumors because HLA antigens mediate interactions of tumor cells with the host's immune system.


METHODS
Eighty-eight surgically removed malignant astrocytic tumors, classified according to the WHO criteria, were stained in immunoperoxidase reactions with monoclonal antibody recognizing monomorphic, locus-specific, and allospecific determinants of HLA class I antigens, beta2-microglobulin, APM components (LMP2, LMP7, TAP1, TAP2, calnexin, calreticulin, and tapasin), and HLA class II antigens.


RESULTS
HLA class I antigens were lost in approximately 50% of the 47 glioblastoma multiforme (GBM) lesions and in approximately 20% of the 18 grade 2 astrocytoma lesions stained. Selective HLA-A2 antigen loss was observed in approximately 80% of the 24 GBM lesions and in approximately 50% of the 12 grade 2 astrocytoma lesions stained. HLA class I antigen loss was significantly (P < 0.025) correlated with tumor grade. Among the APM components investigated, tapasin expression was down-regulated in approximately 20% of the GBM lesions analyzed; it was associated, although not significantly, with HLA class I antigen down-regulation and tumor grade. HLA class II antigen expression was detected in approximately 30% of the 44 lesions analyzed.


CONCLUSIONS
The presence of HLA antigen defects in malignant brain tumors may provide an explanation for the relatively poor clinical response rates observed in the majority of the T cell-based immunotherapy clinical trials conducted to date in patients with malignant brain tumors.
Facoetti
Angelica
A
Department of Animal Biology, University of Pavia and Center of Study for Histochemistry, Consiglio Nazionale delle Ricerche, Italy.
Nano
Rosanna
R
Zelini
Paola
P
Morbini
Patrizia
P
Benericetti
Eugenio
E
Ceroni
Mauro
M
Campoli
Michael
M
Ferrone
Soldano
S
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000911:Antibodies, Monoclonal; D017951:Antigen Presentation; D017920:Antiporters / Q000378:metabolism*; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D037281:Calnexin / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015536:Down-Regulation; D015789:HLA-A2 Antigen / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D001613:beta 2-Microglobulin / Q000378:metabolism
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D017920:Antiporters; D014408:Biomarkers, Tumor; D037282:Calreticulin; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D009097:Multienzyme Complexes; C073119:TAP1 protein, human; D001613:beta 2-Microglobulin; C107762:tapasin; D037281:Calnexin; C071313:LMP-2 protein; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex