Anti-CD40 antibody and toll-like receptor 3 ligand restore dendritic cell-mediated anti-tumor immunity suppressed by morphine
Journal
American Journal of Cancer Research
Journal Volume
157
Journal Issue
172
Pages
157-172
Date Issued
2016
Author(s)
Chang M.-C.
Jen Y.-W.
Abstract
The influence of morphine on host immunity and the underlying mechanism are still unclear. In the current study, we investigated the influence of morphine on dendritic cells (DCs), its possible mechanism of action, and the molecules that could reverse these effects. Morphine suppressed DC maturation, antigen presenting abilities, and the ability to activate antigen-specific CD8+ T cells. Morphine-treated DCs also secreted higher concentrations of IL-10, but lower IL-6 and TNF-a. Morphine-treated DCs showed decreased ERK1/2 phosphorylation and reduced p38 dephosphorylation. The in vivo administration of immuno-modulators, anti-CD40 Ab and TLR3 ligand-poly(I:C), enhanced antigen-specific immunity, promoted the anti-tumor effects, and prolonged the survival of morphine-treated, tumor-bearing mice by promoting the maturation and function of BMM-derived DCs by enhancing ERK1/2 phosphorylation and p38 dephosphorylation. We concluded that morphine can inhibit DC-mediated anti-tumor immunity by suppressing DC maturation and function. Immuno-modulators, such as anti-CD40 Abs and TLR agonists, can restore the DC-mediated anti-tumor immunity. Use of immuno-modulators could serve as a useful approach to overcome the immunocompromised state generated by morphine.
SDGs
Other Subjects
antibody; CD40 antibody; immunomodulating agent; interleukin 10; interleukin 6; lipopolysaccharide; mitogen activated protein kinase 1; mitogen activated protein kinase 3; morphine; polyinosinic polycytidylic acid; synaptophysin; toll like receptor 3; tumor necrosis factor alpha; unclassified drug; animal cell; animal experiment; animal model; animal tissue; antigen presentation; antineoplastic activity; Article; cancer survival; CD8+ T lymphocyte; cellular immunity; controlled study; dendritic cell; drug effect; enzyme linked immunosorbent assay; enzyme linked immunospot assay; enzyme phosphorylation; female; flow cytometry; in vitro study; in vivo study; monocyte; mouse; nonhuman; ovary cancer; protein dephosphorylation; tumor immunity; Western blotting
Type
journal article