Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro

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dc.citation.spagee1921927
dc.citation.volume13
dc.contributor.authorRadojević, Dušan
dc.contributor.authorTomić, Sergej
dc.contributor.authorMihajlović, Dušan
dc.contributor.authorTolinački, Maja
dc.contributor.authorPavlović, Bojan
dc.contributor.authorVučević, Dragana
dc.contributor.authorBojić, Svetlana
dc.contributor.authorGolić, Nataša
dc.contributor.authorČolić, Miodrag
dc.contributor.authorĐokić, Jelena
dc.date.accessioned2023-06-07T09:40:33Z
dc.date.available2023-06-07T09:40:33Z
dc.date.issued2021
dc.description.abstractAlthough promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated in vitro display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals’ immune responses, but it is unknown how it affects the variability of donors’ precursor cells to differentiate into immunogenic DCs in vitro. By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Namely, donors who had higher α-diversity of gut microbiota and higher abundance of short-chain fatty acid (SCFAs) and SCFA-producing bacteria in feces, displayed lower expression of CD1a on immature (im)DC and higher expression of ILT-3, costimulatory molecules (CD86, CD40) proinflammatory cytokines (TNF-α, IL-6, IL-8) and IL-12p70/IL-10 ratio, all of which correlated with their lower maturation potential and immunogenicity upon stimulation with LPS/IFNγ, a well-known Th1 polarizing cocktail. In contrast, imDCs generated from donors with lower α-diversity and higher abundance of Bifidobacterium and Collinsella in feces displayed higher CD1a expression and higher potential to up-regulate CD86 and CD40, increase TNF-α, IL-6, IL-8 production, and IL-12p70/IL-10 ratio upon stimulation. These results emphasize the important role of gut microbiota on the capacity of donor precursor cells to differentiate into immunogenic DCs suitable for cancer therapy, which could be harnessed for improving the actual and future DC-based cancer therapies.
dc.identifier.doi10.1080/19490976.2021.1921927
dc.identifier.urihttps://vaseljena.ues.rs.ba/handle/123456789/294
dc.language.isoen
dc.sourceGut Microbes
dc.subjectGut microbiota; SCFA; monocyte derived dendritic cells; anti-cancer vaccine; myeloid cell therapy
dc.titleFecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro
dc.typeArticle
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