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Human leukocyte antigen and antigen
processing machinery component defects in astrocytic tumors
Facoetti A, Nan R, Zelini P, Morbini P, Benericetti
E, Ceroni M, Campoli M, Ferrone S
Department of Animal Biology, University of Pavia and Center of
Study for Histochemistry, Consiglio Nazionale delle Ricerche, Italy
Purpose. 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.
Experimental Design.
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.
Conclusion. 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.
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