Immunobiological and experimental aspects of malignant astrocytoma

Today several findings indicate that a multifactorial strategy is the best strategy for treating cancer. Although radiotherapy, chemotherapy and surgery have been differently applied to treat human gliomas, no substantial improvement in life expectancy has been observed. Starting from 1992, the goal of our studies was to obtain new biological data on malignant astrocytomas to better understand the basic biology of the tumour and these are reviewed here. Immunotherapy may represent an available method in addition to the traditional therapeutic approaches. Starting from 1991, we set up a cellular model of lymphocytes obtained from peripheral blood of healthy patients treated with interleukin-2 (IL-2) in order to study the role of IL-2 in regulating lymphocytes activation. The lymphocytes responding to IL-2 treatment, named lymphokine-activated killer (LAK) cells, have a killer non MHC restricted activity, and are able to kill autologous and allogenic glioma cells. The interaction of LAK cells with various normal and transformed targets indicates that LAK cells recognize surface structures present both on normal and transformed cells. However, only the interaction with transformed cells induces lytic events and LAK cells can act as "surgical weapons" against tumour cells independently from their cell cycle. Much recent effort has focused on identifying the immune escape mechanisms used by glioma cells, in particular the modulation of the human leukocyte antigen (HLA) and antigen processing machinery component expression. Finally, another interesting field of research that will be presented is that of new tumour biomarkers of proliferation and apoptosis, cytokine/chemokine release and cytokine/chemokine receptors.