Therefore, it is conceivable that TNF-alpha, similar to IFN-gamma, might provoke tumor rejection not only via direct tumoricidal action but also via enhancement of HLA antigens and induction of tumor-specific immune responses.
Thus we present evidence that in colorectal cancer only a small proportion of tumor-infiltrating macrophages produces TNF, indicating that the microenvironment of the tumor provides adequate, yet suboptimal, conditions for macrophage activation.
The production of TNF by human ovarian cancer cells may influence the biology of the tumour, contribute to neoplastic progression and alter the response to therapy.
IL-2-expanded 444P.3 cells, tested on day 104 in culture, expressed mRNA for tumor necrosis factor (TNF), IL-2 and tumor growth factor beta (TGF-beta) but not for IL-1, lymphotoxin or granulocyte/macrophage-colony stimulating factor (GM-CSF).
Viruses or virally infected cells (including tumor cells) induce the production of lymphokines and cytokines (interferons, interleukins and tumor necrosis factor) and activate NK cells and specific immune T cells cytotoxic to virus-infected cells (including tumor cells).7.
A regulatory factor isolated from the maternal part of bovine placentas (decidua inhibitory factor, DIF) inhibits the incorporation of thymidine into the DNA of a variety of animal and human tumors.
A co-cultivated tumor model prepared from other types of human tumor cell lines promises to provide a useful tool for exploring the relationship between TNF-alpha/cachectin and oncogenesis.
After in vitro incubation of melanoma tumour cells Cmel453A with either recombinant interferon gamma (rIFN-gamma) or tumour necrosis factor alpha (rTNF-alpha) a dose-dependent inhibition of cell growth occurred; when both cytokines were added, a synergistic action was observed.
The addition of tumor necrosis factor alpha (TNF alpha) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P less than 0.05).
This study employed the tumor-necrosis-factor(TNF)-sensitive U937 tumor cell line as a model system to determine if selection of a tumor cell variant for cytokine resistance would also result in drug resistance and vice versa.
Interestingly, the primary tumor C15 showed a profile of TNF-sensitive tumor while C17, C18 and C19 which were derived from metastasis have a typical profile of TNF-resistant cells.
Analysis of frozen sections of tumour biopsy specimens revealed variable degrees of macrophage infiltration and great heterogeneity in TNF gene expression.
Clinical trials based on these observations have begun in which patients are immunized against their own autologous tumors that were transduced with the genes for TNF or interleukin-2.
TNF mRNA was found in epithelial tumor cells and infiltrating macrophages, whereas TNF protein localized primarily to a subpopulation of macrophages within and in close proximity to tumor areas. mRNA and protein for the p55 TNF receptor gene localized to the tumor epithelium and tumor, but not to stromal macrophages.