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Naturally produced type I IFNs enhance human myeloid dendritic cell maturation and IL-12p70 production and mediate elevated effector functions in innate and adaptive immune cells. | LitMetric

AI Article Synopsis

  • Recent research has highlighted a shift towards using directly isolated human blood-derived dendritic cells (DCs) in immunotherapy, proving more effective than lab-grown versions.
  • The two main DC types studied, plasmacytoid DCs (pDCs) and myeloid DCs (mDCs), show distinct advantages: mDCs are great at presenting antigens and producing IL-12p70, while pDCs excel at triggering immune responses in conditions like melanoma.
  • Combining mDCs and pDCs shows promise as a multi-functional vaccine, as pDCs boost mDC maturation and activity, but the presence of type I interferons (IFNs) can hinder T-cell responses, indicating a careful

Article Abstract

There has recently been a paradigm shift in the field of dendritic cell (DC)-based immunotherapy, where several clinical studies have confirmed the feasibility and advantageousness of using directly isolated human blood-derived DCs over in vitro differentiated subsets. There are two major DC subsets found in blood; plasmacytoid DCs (pDCs) and myeloid DCs (mDCs), and both have been tested clinically. CD1c mDCs are highly efficient antigen-presenting cells that have the ability to secrete IL-12p70, while pDCs are professional IFN-α-secreting cells that are shown to induce innate immune responses in melanoma patients. Hence, combining mDCs and pDCs poses as an attractive, multi-functional vaccine approach. However, type I IFNs have been reported to inhibit IL-12p70 production and mDC-induced T-cell activation. In this study, we investigate the effect of IFN-α on mDC maturation and function. We demonstrate that both recombinant IFN-α and activated pDCs strongly enhance mDC maturation and increase IL-12p70 production. Co-cultured mDCs and pDCs additionally have beneficial effect on NK and NKT-cell activation and also enhances IFN-γ production by allogeneic T cells. In contrast, the presence of type I IFNs reduces the proliferative T-cell response. The mere presence of a small fraction of activated pDCs is sufficient for these effects and the required ratio between the subsets is non-stringent. Taken together, these results support the usage of mDCs and pDCs combined into one immunotherapeutic vaccine with broad immunostimulatory features.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132867PMC
http://dx.doi.org/10.1007/s00262-018-2204-2DOI Listing

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