o:25584 Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells in vitro Sastav fekalne mikrobiote povezuje se sa sposobnošću monocita periferne krvi čoveka da se diferenciraju u imunogene dendritske ćelije in vitro en ABSTRACT Although 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. Gut microbiota, SCFA, monocyte derived dendritic cells, anti-cancer vaccine, myeloid cell therapy 1552099 10.1080/19490976.2021.1921927 2022-05-23T16:19:45.263Z 44 yes 46 Dušan Radojević University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Microbiology, Serbia Jelena Đokić University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Microbiology, Serbia person Miodrag Čolić Serbian Academy of Sciences and Arts, Belgrade, Serbia akademik person Nataša Golić University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Microbiology, Serbia person Svetlana Bojić HITTest d.o.o, Belgrade, Serbia person Dragana Vučević University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia person Bojan Pavlović PHYTONET d.o.o, Belgrade, Serbia person Maja Tolinački University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Microbiology, Serbia person Dušan Mihajlović University of Defence, Medical Faculty of the Military Medical Academy, Belgrade, Serbia person Sergej Tomić University of Belgrade, Institute for the Application of Nuclear Energy INEP, Serbia doktor bioloških nauka person 0000-0003-2570-1295 application/pdf 2615176 https://phaidrabg.bg.ac.rs/o:25584 no yes 16 70 92000001 11A26 11A2602 11A29 11A2904 Gut Microbes 13 1 Taylor & Francis Group, LLC 2021