IN-VITRO STUDIES OF CYTOKINE-MEDIATED INTERACTIONS BETWEEN MALIGNANT GLIOMA AND AUTOLOGOUS PERIPHERAL-BLOOD MONONUCLEAR-CELLS

The humoral interactions between three malignant glioma early-passage cell cultures and in vitro interleukin (IL)-1 alpha- and IL-2-activate d autologous peripheral blood mononuclear cells (PBMC's) were investig ated, employing standard and modified (separated by permeable membrane s) mixed lymphocyte tumor cell (MLTC) cultures. In modified MLTC's, gl ioma cells clearly inhibit proliferation of PBMC's (up to 60%), wherea s lymphokine-activated PBMC's enhance glioma cell growth up to 12-fold , as determined by H-3-thymidine incorporation assays; Glioma cells pr oduce both stimulatory (IL-6) and inhibitory proteins (transforming gr owth factor-beta) for PBMC's. Lymphokine-activated PBMC's secrete IL-1 alpha, IL-2, IL-4, IL-6, interferon-gamma, and tumor necrosis factor- alpha, which may modulate glioma cell proliferation. None of these cyt okines stimulated glioma cells as intensely as modified MLTC systems. These observations indicate that in vitro lymphokine-activated PBMC's, although suppressed by humoral glioma-derived factors, may enhance gl ioma cell proliferation with soluble factors secreted into the culture medium. The authors conclude that glioma-lymphocyte growth regulatory networks include stimulatory and inhibitory factors from both cell po pulations, which may modulate tumor progression. These observations ma y have relevance for adoptive immunotherapy in patients with gliomas.