Soluble factors, including TNF alpha, secreted by human T cells are both cytotoxic and cytostatic for medulloblastoma cells

We studied the effect of the treatment of a medulloblastoma cell line by hu man T cells derived soluble factors. Medulloblastoma is one of the more com mon aggressive solid neoplasms in children for which there is no adequate t herapy. Cell lines established from such tumours may be helpful to test the effect of various molecules on cell proliferation. Previous studies have s uggested that T cell-derived factors may be toxic for the medulloblastoma c ell line Dev. Cytokines were thought to mediate this effect. In this paper, we described changes in morphology, survival and cell cycle induced in Dev cells cocultured with human T cell lines chronically infected with a retro virus (HTLV-I) and known to secrete high level of cytokines TNF alpha, IL1 alpha and IL6. Such cocultures resulted in the death of a part of Dev cells and in decreased proliferation of surviving cells, associated with morphol ogical changes and increase in vimentin expression. Treatment with conditio ned medium from infected Dev cells, containing virus induced cytokines, tri ggered the same effect. Reduction of these effects by TNF alpha deprivation of conditioned medium suggested that this cytokine may be implicated. Dire ct treatment of Dev cells with recombinant cytokines indicated that TNF alp ha, but not IL1 or IL6, is associated with Dev cell alterations. TNF alpha was shown to induce the death of Dev cells by an apoptotic pathway. Further more, TNF alpha had a bimodal effect on the cell cycle of surviving Dev cel ls. These differential effects of such cytokines on medulloblastoma cells c ould be therefore of interest for immunotherapy of these tumours.