Transduction of human melanoma cell lines with the human interleukin-7 gene using retroviral-mediated gene transfer: comparison of immunologic properties with interleukin-2

Abstract

Two human melanoma cell lines were transduced with the human interleukin (IL)-7 and IL-2 genes using retroviral-mediated gene transfer. Stable, high-level cytokine expression was achieved. The in vitro growth of transduced tumors was unaltered. Neither of the IL-2- transduced melanoma cell lines grew in athymic mice, whereas one IL-7- transduced melanoma line showed retarded in vivo growth. This is consistent with animal studies suggesting a predominantly T-cell response to IL-7-transduced tumors and a more nonspecific response to IL-2-transduced tumors. Both IL-7- and IL-2-transduced melanoma cell lines could induce cytotoxic lymphocytes in mixed lymphocyte-tumor cultures. The expression of putative melanoma antigens (MAGE)-1 and MAGE-3 was unaltered by cytokine transduction. In one cell line, IL-7 transduction resulted in a marked inhibition of the immunosuppressive peptide transforming growth factor (TGF)beta 1. The results allow a comparison of immunobiologic properties of IL-7- and IL-2-transduced human melanoma cell lines in consideration of their use in genetically engineered tumor vaccines. IL-7 transduction results in stable cytokine expression and phenotypic alterations that appear to be favorable for enhanced immunogenicity and it deserves clinical testing.

IL-7 inhibits fibroblast TGF-β production and signaling in pulmonary fibrosis

“…Overexpression of TGF-β contributes to the dysregulation of the normal homeostasis at multiple levels: it enhances synthesis and deposition of ECM components including collagen and can also alter the balance of matrix metalloproteinases and their inhibitors (24,25,(30)(31)(32)(33)(34). Based on the importance of TGF-β in the pathogenesis of pulmonary fibrosis, in the current study IL-7 was chosen for evaluation, because we have previously found that IL-7 downregulates macrophage (14), fibrosarcoma, and melanoma (15,16) production of TGF-β.…”

“…Monoclonal anti-TGF-β antibody measures TGF-β1, 2, and 3. ELISA was performed based on a horseradish peroxidase method as described previously ( [14][15][16]. OD of each sample after color development was determined with a microplate reader (Dynatech Laboratories, Chantilly, Virginia, USA) at 450 nm.…”

Induction of T helper 17 cell response by interleukin-7 in patients with primary cutaneous melanoma

“…Phosphorylated STAT5 mediates the transcription of antiapoptotic genes, especially B cell lymphoma-2 (Bcl-2) [10][11][12]. Previous studies showed that recombinant IL-7 stimulation or IL-7-expressing plasmid transduction results in the phenotypic alteration and stable cytokine expression by human malignant melanoma cell lines, revealing the potential enhancement of immunogenicity [13,14]. However, the role of IL-7 in regulation of immune cells was not completely understood.…”

IL-7 is a Key Driver Cytokine in Spondyloarthritis?

“…Indeed, the ability of TGF- β to inhibit IL-7-induced pre-B cell proliferation was recognized shortly after identification of IL-7. While the mechanisms and implications of this antagonistic correlation are not yet well clarify, the potential role of these two molecules in several cell populations of immunity suggests that this interaction has important influence on immunological regulation [2, 43].…”