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

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 host9s 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, β 2 -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 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.