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Human Leukocyte Antigen and Antigen Processing Machinery Component Defects in Astrocytic Tumors

Authors' Affiliations: ¹ Department of Animal Biology, University of Pavia and Center of Study for Histochemistry, Consiglio Nazionale delle Ricerche; ² Department of Pathology, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo; ³ Department of Neurological Sciences, Istituto di Ricovero e Cura a Carattere Scientifico C. Mondino Institute, University of Pavia, Pavia, Italy; ⁴ Neurosurgery Division, Hospital of Parma, Parma, Italy; ⁵ Policlinico of Monza, Monza, Italy; and ⁶ Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York

Requests for reprints: Soldano Ferrone, Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. Phone: 716-845-8534; Fax: 716-845-7613; E-mail: soldano.ferrone{at}roswellpark.org.

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, ß₂-microglobulin, APM components (LMP2, LMP7, TAP1, TAP2, calnexin, calreticulin, and tapasin), and HLA class II antigens.

Results: HLA class I antigens were lost in 50% of the 47 glioblastoma multiforme (GBM) lesions and in 20% of the 18 grade 2 astrocytoma lesions stained. Selective HLA-A2 antigen loss was observed in 80% of the 24 GBM lesions and in 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 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 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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