Immunobiology of malignant gliomas

The immune system of patients with malignant gliomas is profoundly suppressed. The suppression involves both the cellular and humoral immunity and it is mainly attributable to selective depletion and malfunction of helper T cells. Malignant glioma cells express potent immunosuppressive factors such as transforming growth factor-beta(2), inteleukin-10 and prostaglandin E(2). Malignant glioma cells also produce chemoattractants and immunostimulatory cytokines which may activate the immune cells. However, the production of these stimulatory cytokines is not self-destructive to glioma cells because of the immunosuppression. Rather, the tumour cells use them to gain a growth advantage. Indeed the cytokines may act as a growth stimulator of the tumour cells themselves (autocrine mechanism), they may act as angiogenic factors to endothelial cells (paracrine mechanism) or induce the attracted immune cells to secrete angiogenic factors. Some cytokines produced by malignant glioma cells are known to be growth inhibitory to normal astrocytes. Recent studies on tumour suppressor genes suggest a close link between the aberrant genes and the immunobiologic features of malignant glioma cells.