Effects of recombinant human tumor necrosis factor‐α on the surface phenotype and the growth of human malignant glioma cell lines

Abstract

Human malignant glioma cell lines and clones were incubated with various concentrations of recombinant human TNF-alpha, either alone or in combination with recombinant human IFN-gamma. The surface expression of HLA-ABC (class I) antigens and beta 2-microglobulin, was significantly enhanced by TNF-alpha alone on every cell line and clone tested. After incubation with both TNF-alpha and IFN-gamma, the surface expression of HLA-ABC antigens was only slightly higher than that observed with each cytokine alone. In contrast to IFN-gamma, TNF-alpha had no effect on the surface expression of HLA-DR (class II) antigens. Moreover, the surface expression of HLA-DR induced by IFN-gamma was unaffected by TNF-alpha. The increased expression of HLA-ABC antigens after treatment with TNF-alpha or IFN-gamma correlated with increased levels of HLA-ABC-specific mRNA. In addition, TNF-alpha, like IFN-gamma, selectively enhanced the surface expression of a tumor-associated antigen, Me14-D12, while it had no effect on the expression of various other surface antigens. In the absence of actinomycin D, TNF-alpha exhibited no direct cytotoxic/cytostatic effect on the glioma cell lines tested. These results indicate that TNF-alpha can enhance the surface expression of HLA-ABC antigens on human glioma cells in the absence of a direct cytotoxic/cytostatic effect.

Cytokine‐mediated modulation of HLA‐class II, ICAM‐1, LFA‐3 and tumor‐associated antigen profile of melanoma cells. comparison with anti‐proliferative activity by RIL1‐β, RTNF‐α, RIFN‐γ, RIl4 and their combinations

“…The concentration of 500 Ulml was chosen on the basis of preliminary dose-response experiments showing that lower doses of the different cytokines were often ineffective (data not shown) and with the aim of comparing our results with other studies using cytokines in the same range of concentrations (Collins et al, 1986;Anichini et al, 1988;Rousset et al, 1988;Zuber et al, 1988). The melanomas were then evaluated for changes in cell-surface expression of HLA-DR, DP and 3 different MAAs.…”

Cytokines in chronic inflammatory arthritis. V. Mutual antagonism between interferon-gamma and tumor necrosis factor-alpha on HLA-DR expression, proliferation, collagenase production, and granulocyte macrophage colony-stimulating factor production by rheumatoid arthritis synoviocytes.

“…Examples of this phenomenon include the induction of HLA-DR molecules on a murine macrophage cell line (36) and various human tumor cell lines (37)(38)(39); induction of chemotactic peptide receptor expression on HL-60 cells (a human promyelocytic cell line) (40); induction of class I MHC molecules on human glioma tumor cells (41); induction ofglycosaminoglycan synthesis by human lung fibroblasts (42); and increased production of collagen by dermal fibroblasts (43). TNF-alpha inhibits IFN-gamma-mediated induction ofclass II MHC molecules on human umbilical vein endothelial cells (44), but the fact that this combination is also cytotoxic on those cells (30) makes the interpretation of those data difficult.…”

Adenovirus‐mediated Gene Transduction of IkB or IkB Plus Bax Gene Drastically Enhances Tumor Necrosis Factor (TNF)‐induced Apoptosis in Human Gliomas

“…3) However, TNF does not exhibit a direct cytotoxic effect on most glioma cell lines. [4][5][6] Instead, TNF promotes the growth of U-373 glioma cells. 7) Therefore, conventional therapies such as radiation, [8][9][10] chemotherapy 11) and immunotherapy 12,13) have been used in combination with TNF treatment to augment the therapeutic effect in patients with malignant gliomas.…”