title: Anti-CD40 antibody and toll-like receptor 3 ligand restore dendritic cell-mediated anti-tumor immunity suppressed by morphine.
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-α. 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.
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan UniversityTaipei, Taiwan; Department of Anesthesiology, College of Medicine, National Taiwan UniversityTaipei, Taiwan.
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University Hospital HsinChu Branch, HsihChu, Taiwan.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Ying-Cheng
authors.initials: YC
authors.lastname: Chiang
authors.affiliation: Department of Anesthesiology, College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Ya-Jung
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, Cathay General Hospital Taipei, Taiwan.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Jen
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Chi-An
authors.initials: CA
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, National Taiwan UniversityTaipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan UniversityTaipei, Taiwan; Graduate Institute of Oncology, College of Medicine, National Taiwan UniversityTaipei, Taiwan.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, College of Medicine, National Taiwan UniversityTaipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan UniversityTaipei, Taiwan.
authors.forename: Wei-Zen
authors.initials: WZ
authors.lastname: Sun
keywords: ERK1/2 transduction pathway; Morphine; anti-tumor effects; antigen presenting cells; antigen processing; dendritic cells; immune-modulator; immunosuppression; p38 transduction pathway