Ex vivo recovery and activation of dysfunctional, anergic, monocyte-derived dendritic cells from patients with operable breast cancer: critical role of IFN-alpha
| Autor: | Sukchai Satthaporn, Alasdair J Mckechnie, Mark M. Aloysius, Chandan Verma, Mohamad El-Sheemy, David Clark, Richard A Robins, David Valerio, Oleg Eremin, Suebwong Chuthapisith, Jibril A Jibril, Wichai Vassanasiri |
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| Rok vydání: | 2007 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
Allergy Immunology Alpha interferon Breast Neoplasms Receptors Cell Surface Biology Immunophenotyping Breast cancer Immune system medicine Humans Lectins C-Type Lymphocytes Cells Cultured Mannan-binding lectin Pinocytosis Interferon-alpha Dendritic Cells medicine.disease Mannose-Binding Lectins Culture Media Conditioned Cytokines B7-2 Antigen lcsh:RC581-607 Ex vivo Mannose Receptor Research Article |
| Zdroj: | BMC Immunology BMC Immunology, Vol 9, Iss 1, p 32 (2008) |
| ISSN: | 1471-2172 |
| Popis: | Background Dendritic cells (DCs) play a crucial role in initiating effective cell-mediated immune responses, but are dysfunctional and anergic in breast cancer. Reversal of this dysfunction and establishment of optimal DC function is a key prerequisite for the induction of effective anti-cancer immune responses. Results Peripheral blood DCs (PBDCs) and lymph node DCs (LNDCs) generated in vitro from adherent cultures of peripheral blood monocytes (PBMs) and lymph node monocytes (LNMs), respectively, using the 4 cytokine conditioned medium (CCM) (GM-CSF+IL-4+TNF-α+IFN-α) or 3 CCM (GM-CSF+IL-4+TNF-α) demonstrated a significantly higher degree of recovery and functional capacity in a mixed lymphocyte DC reaction (MLDCR, p < 0.001), expressed significantly higher levels of HLA-DR, CD86, compared with 2 CCM (GM-CSF+IL-4) or medium alone generated DCs from PBMs and LNMs (p < 0.001). The PBDCs generated with 3 CCM or 4 CCM showed a significantly (p < 0.001) enhanced macropinocytotic capability (dextran particles) and induced increased production and secretion of interleukin-12p40 (IL-12p40) in vitro (p < 0.001), compared with PBDCs generated from monocytes using 2 CCM or medium alone. Lipopolysaccharide (LPS) stimulation of PBDCs generated with 4 CCM demonstrated enhanced secretion of IL-6 but not IL-12p70, compared with control DCs unstimulated with LPS (p < 0.001). Conclusion Dysfunctional and anergic PBDCs and LNDCs from patients with operable breast cancer can be optimally reversed by ex vivo culturing of precursor adherent monocytes using a 4 CCM containing IFN-α. Maximal immunophenotypic recovery and functional reactivation of DCs is seen in the presence of IFN-α. However, 4 CCM containing IFN-α generated-PBDCs, do not produce and secrete IL-12p70 in vitro. |
| Databáze: | OpenAIRE |
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