WHO Grade Our Designation Description 
1 Pilocytic astrocytoma - Astrocytoma comprised predominantly of piloid 
cells with or without a biphasic pattern. Endothelial 
proliferation often present, as are Rosenthal fibers and 
protein granular bodies. Mitoses only within 
endothelial cell population. Necroses absent. 
2 Astrocytoma Diffuse increase in non-reactive astrocytes (high 
nuclear/ cytoplasmic ratio) with mild to moderate 
atypia. Clusters of undifferentiated tumor cells, 
mitoses, endothelial proliferation & necrosis 
are absent. 
3 Anaplastic 
Astrocytoma 
4 Glioblastoma 
Multiforme 
Features of astrocytoma, plus clusters of undifferentia- 
ted tumor cells, marked nuclear and cytoplasmic 
pleomorphism and mitotic figures. Endothelial 
proliferation and necrosis absent. 
Features of anaplastic astrocytoma plus endothelial 
proliferation and/or necrosis. 
The distinction between low grade and high grade gliomas is important for determining 
prognosis and treatment since patients with low grade astrocytomas often have a mean survival time 
measured in years and are frequently treated by surgery alone. Patients with high grade gliomas have 
a mean survival time of less than a year and failure is due to tumor progression despite aggressive 
therapy. Although patients with anaplastic astrocytoma may have a more variable course than those 
with gioblastoma, ultimately recurrence or progression to glioblastoma multiforme is the rule. 
- Research Background and Rationale for Study 
Tumor Immunolog y Tumors produce remote effects on the immune system which 
promote growth of the tumor. Mechanisms which have been invoked to explain these effects include 
production of suppressor factors by the tumor and diminished production of cytokines (17,18). Malignant 
gliomas (which develop and grow locally in the brain) are partially sequestered from the immune 
system, yet they are associated with marked systemic suppression of humoral and cell-mediated 
immunity (19). Peripheral blood lymphocytes from patients with glioma respond poorly to mitogens 
and/or antigens, and the percentage and absolute numbers of peripheral blood T cells are decreased (20). 
IL-2 production by lectin stimulated T cells is significantly less than that by T cells from normals. 
Activated T cells from patients with glioma have a defect in the expression of high affinity IL-2 
receptors. A defect in helper-cell function may also explain the known clinical failure of glioma 
patients to mount antibody responses to influenza virus and tetanus toxoid. A T cell suppressor factor 
present in the sera of patients with glioma has been described (21). More recent work isolating and 
characterizing glioblastoma-derived T cell suppressor factors have identified the TGF-fis as a 
mediator of this action. TGF-P 2 which is elaborated by malignant gliomas has been shown to inhibit T 
cell proliferation in vitro by IL-1 dependent mechanisms (22,23). Immunosuppressive mediators 
produced by glioma cells in culture induce cellular and biochemical dysfunction in immune cells (24). 
RNA for TGF-Ps have been identified in most glioblastomas (25). 
Efforts to enhance immunity as a way of treating astrocytoma and glioblastoma have 
not been effective, possibly because of immune suppression produced by the tumor (26). Partial 
amelioration of T cell suppression, after surgical resection of the glioblastoma has been observed 
clinically (27). A variety of strategies have been tried, from non-specific enhancement of the immune 
response by interferon and interleukin-2, to injection of activated lymphocytes (17) and monoclonal 
[132] Recombinant DNA Research, Volume 18 
