Interferon gamma (IFN-gamma) is the most potent known lymphokine for activating macrophages and has been shown to induce expression of HLA-DR in THP-1 cells, a monocytic tumor cell line which expresses many of the properties of monocytes, in a dose- and time-dependent manner.
Therefore, the highly differentiated LS174T cell line and the poorly differentiated MIP cell line represent colorectal tumor cell types that are unresponsive to the ability of IFN-gamma to induce alterations in tumor (i.e., CEA) or normal (i.e., class I and class II human leucocyte antigen) surface antigen expression.
Distinct effects of interferon-gamma and MHC class I surface antigen levels on resistance of the K562 tumor cell line to natural killer-mediated lysis.
Thus, the effect of the combined TNF-alpha and IFN-gamma therapy involved the selective destruction of the tumour vasculature, death of tumour cells and increased expression of a series of stromal cytokines, cytokine receptors and adhesion molecules, which could be implicated in the observed events.
Retroviral transfer of the IFN gamma gene was associated with decreased growth, decreased tumor invasiveness, IFN gamma production, and upregulation of MHC antigens.
Granulocyte-macrophage colony stimulating factor secreting tumor cell preparations were less effective, and interferon-gamma secreting cells had only a marginal effect.
A primary tumor cell line was generated and cultured TIL were induced to transcribe IL-2 and IFN-gamma genes by incubation with the autologous irradiated tumor cell line, but not with autologous EBV-transformed cells.
Three human tumour cell lines, A431 (cervical), Scaber (bladder) and Fen (bladder), were studied using immunohistochemical staining (IC), radiobinding (RB), immunoprecipitation (IP), enzyme-linked immunosorbent assay (ELISA) and dot-blot (DB) techniques in order to assess major histocompatibility antigen (MHC) induction in response to interferon-gamma (IFN-gamma).
Mezerein-differentiated THP-1 cells secrete interleukin-1 beta as well as a tumor cell growth inhibitory factor whose basal level is increased in response to interferon-gamma.
The therapeutic effect of IFN-gamma-secreting cells was minimal and treatment with unmodified MBT-2 cells had no effect on tumor growth or survival, showing that the parental MBT-2 cells were nonimmunogenic in this experimental setting.
In this study a retroviral vector was used to introduce the IFNgamma gene into EMT6 tumor cells to assess the effect of IFNgamma gene expression on tumor immunogenicity.
During BCG treatment, we analyzed induction of IL-2 and IFN-gamma mRNA in peripheral-blood mononuclear cells (PBMC) from 73 patients: 51 with papillary tumors and 22 with carcinoma-in-situ (CIS).
We assessed TIL expression of interleukin-2 (IL-2), IL-4, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), granulocyte-macrophage colony stimulating factor (GM-CSF), IL-10, and transforming growth factor-beta (TGF-beta), and tumor cell expression of IL-10 and TGF-beta in situ in 49 primary colon carcinomas and 20 metastases using immunohistochemistry.
The results support a shift towards Th 1 (T helper 1) cells and interferon-gamma production, and that IL-12 also in vivo may play an important role in the regulatory interaction between innate resistance and adaptive immunity in tumour diseases.
Two different transgenic mice showed identical expression of interleukin-1alpha (IL-1alpha), IL-1beta, interferon gamma (IFNgamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in peripheral tail tumors.
Mononuclear cells from paired blood samples from fifteen patients with myasthenia gravis before and after thymectomy and immunosuppressive therapy were examined by in situ hybridization for acetylcholine receptor-induced mRNA expression of the T helper type 1 proinflammatory cytokines interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha) and TNF-beta, the T helper type 2 cytokines interleukin 4 (IL-4) and IL-10 and the immune response downregulating cytokine tumor growth factor beta (TGF-beta).
Experimental data derived from mouse B16 malignant melanoma models indicates that the weight of tumor in mice treated with IFN fusion proteins was significantly smaller than that of mice treated with interferon-gamma alone.
IL-2 gene-transduced NK-92 cells had an in vitro cytotoxicity against tumor targets that was significantly higher than that of parental cells and secreted interferon gamma (IFNgamma) and tumor necrosis factor alpha (TNFalpha) in addition to IL-2.
Using this approach, the median survival of tumor bearing nude mice was prolonged by the administration of a human tumor necrosis factor-alpha (TNF-alpha) gene inserted into a eukaryotic strong expression vector (pcagTNF-alpha) and exogenously added interferon-gamma (INF-gamma) (72 +/- 3 days: mean +/- s.e.).
We have found that (i) established EOC tumour cell lines expressed transcripts for transforming growth factor-beta 2 (TGF-beta2) (7/7), but not IL-10 (0/7) or interferon-gamma (IFN-gamma) (0/7) and rarely IL-2 (1/7); (ii) PEC expressed transcripts for IL-2 (12/13), IL-10 (9/13), and TGF-beta2 (12/13), and less often, IFN-gamma (3/13), whereas solid tumour specimens from eight patients with EOC expressed transcripts for IL-2 (4/8), TGF-beta2 (4/8), and IL-10 (5/8), but not for IFN-gamma (0/8); (iii) CD4+ TCRalphabeta+ T cell lines expressed transcripts for IFN-gamma (4/4), IL-2 (4/4) and IL-10 (3/4), whereas CD8+ TCRalphabeta+ T cell lines expressed transcripts for IFN-gamma (5/5), IL-2 (1/5) and IL-10 (2/5).