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-activated autologous peripheral blood mononuclear cells (PBMC's) were investigated, employing standard and modified (separated by permeable membranes) mixed lymphocyte tumor cell (MLTC) cultures. In modified MLTC's, glioma cells clearly inhibit proliferation of PBMC's (up to 60%), whereas lymphokine-activated PBMC's enhance glioma cell growth up to 12-fold, as determined by 3H-thymidine incorporation assays. Glioma cells produce both stimulatory (IL-6) and inhibitory proteins (transforming growth 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 cytokines 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 glioma 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 populations, which may modulate tumor progression. These observations may have relevance for adoptive immunotherapy in patients with gliomas.
Jachimczak
P
P
Department of Neurology, University of Würzburg, Germany.
Schwulera
U
U
Bogdahn
U
U
D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005909:Glioblastoma / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000145:classification; D010641:Phenotype; D014407:Tumor Cells, Cultured
D016207:Cytokines