Immunocytochemical detection of leukocyte-associated and apoptosis-relatedantigen expression in childhood brain tumors

During systematic cell-surface antigen expression profile analyses of 76 pr imary childhood brain tumors [34 medulloblastomas (MED)/primitive neuroecto dermal tumors (PNETs) and 42 astrocytomas (ASTR)], a library of monoclonal antibodies (MoABs) directed against various leukocyte-associated, lymphocyt e cell-line differentiation antigens in childhood brain tumors was utilized . The antigens were detected employing an indirect, biotin-streptavidin con jugated alkaline phosphatase (AP) immunocytochemical technique. Major histo compatibility complex (MHC) class I restricted, tumor-associated antigen (T AA) specific, CD8(+) cytotoxic T lymphocytes (CTL) were identified in 58/76 (76.32%) brain tumors, and usually represented 1-10% of all cells, but in some cases 30-44% of the cells were CD8(+). CD4(+), MHC class II restricted helper lymphocytes were present in 65/76 (85.53%) brain tumors, and accoun ted for 1 - 10% of the observed cells. Macrophages were present in 74/76 (9 7.37%) brain tumors, and their number also represented 1-10% of all observe d cells in the brain tumor frozen sections. Leukocyte common antigen (LCA) expression was detected in all 76 (100%) brain tumors studied. MoAB UJ 308 detected the presence of premyelocytes and mature granulocytes in 60/76 (78 .95%) brain tumors. Natural killer (NK) cells were not defined in the obser ved brain tumors. The great majority of childhood glial tumors, particularl y ASTRs express Fas (APO-1/CD95) receptor whereas normal cells in the centr al nervous system (CNS) do not. FasR is a transmembrane glycoprotein which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. As part of our screening, the 42 childhood ASTRs were also in vestigated for expression of CD95. We detected strong expression (strong in tensity of staining, number of stained cells 50 - 100%) of FasR, employing formalin fixed, paraffin-wax embedded tissue slides. Brain tumors and melan omas have been shown to produce their autocrine Fast. and are even capable of switching CD95-related signal transduction from the PCD pathway to a pro liferative pathway. In view of our results, we conclude that: (I) the tumor infiltrating leukocytes in MEDs/PNETs and ASTRs represent a very diverse p opulation and are present in a great majority of the cases studied; (2) the strong expression of FasR in ASTRs provides a manner in which T lymphocyte s may exert their anti-tumor effects, but may also represent yet another wa y that tumors may evade the immune response and (3) further observations of the expression of various antigens involved in juxtacrine, in situ growth control are necessary for the refinement of cellular immunotherapeutical ap proaches in the treatment of human malignancies. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.