Insulin-like growth factors inhibit dendritic cell-mediated anti-tumor immunity through regulating ERK1/2 phosphorylation and p38 dephosphorylation
Journal
Cancer Letters
Journal Volume
359
Journal Issue
1
Pages
117-126
Date Issued
2015
Author(s)
Abstract
Insulin-like growth factors (IGFs) can promote tumorigenesis via inhibiting the apoptosis of cancer cells. The relationship between IGFs and dendritic cell (DC)-mediated immunity were investigated. Advanced-stage ovarian carcinoma patients were first evaluated to show higher IGF-1 and IGF-2 concentrations in their ascites than early-stage patients. IGFs could suppress DCs' maturation, antigen presenting abilities, and the ability to activate antigen-specific CD8+ T cell. IGF-treated DCs also secreted higher concentrations of IL-10 and TNF-α. IGF-treated DCs showed decreased ERK1/2 phosphorylation and reduced p38 dephosphorylation. The percentages of matured DCs in the ascites were significantly lower in the IGF-1 or IGF-2 highly-expressing WF-3 tumor-bearing mice. The IGF1R inhibitor - NVP-AEW541, could block the effects of IGFs to rescue DCs' maturation and to restore DC-mediated antigen-specific immunity through enhancing ERK1/2 phosphorylation and p38 dephosphorylation. IGFs can inhibit DC-mediated anti-tumor immunity through suppressing maturation and function and the IGF1R inhibitor could restore the DC-mediated anti-tumor immunity. Blockade of IGFs could be a potential strategy for cancer immunotherapy. ? 2015 Elsevier Ireland Ltd.
SDGs
Other Subjects
interleukin 10; mitogen activated protein kinase 1; mitogen activated protein kinase 3; somatomedin; somatomedin B; somatomedin C; synaptophysin; tumor necrosis factor alpha; animal experiment; animal model; animal tissue; antigen specificity; Article; cell assay; cell function; cell maturation; controlled study; cytokine production; dendritic cell; enzyme phosphorylation; enzyme regulation; female; growth inhibition; human; human cell; immune response; molecular dynamics; mouse; nonhuman; ovary cancer; protein dephosphorylation; protein determination; protein expression; protein function; tumor xenograft; Mus
Type
journal article