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The coadministration of trehalose dibehenate and monosodium urate crystals promotes an antitumor phenotype in human‐derived myeloid cells
Author(s) -
Kodar Kristel,
McConnell Melanie J,
Harper Jacquie L,
Timmer Mattie SM,
Stocker Bridget L
Publication year - 2020
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12329
Subject(s) - immune system , cd86 , adjuvant , monocyte , immunology , antigen , mixed lymphocyte reaction , myeloid , major histocompatibility complex , dendritic cell , t cell , chemistry , biology
Trehalose dibehenate (TDB), a ligand for the macrophage‐inducible C‐type lectin, has shown promise as an adjuvant for preventative vaccines and also as an anticancer agent in murine assays. The potential for TDB to affect the antitumor immune response of human myeloid cells, however, has not been studied. We investigated the effect of the adjuvants TDB and monosodium urate (MSU) crystals on the protumor or antitumor immune phenotype of human monocytes, macrophages and monocyte‐derived dendritic cells (Mo‐DCs). TDB treatment alone led to an inflammatory response in all three cell types, which was most pronounced when using human monocytes, with MSU augmenting this response. TDB also decreased cell surface markers associated with a protumorigenic phenotype, with MSU showing some ability to augment this response. Notably, a significant reduction in CD115 was observed for all antigen‐presenting cells upon TDB or MSU + TDB treatment. The potential to increase the antigen‐presenting capabilities of the myeloid cells was also observed upon treatment with TDB and MSU + TDB, as indicated by the upregulation of cell surface markers such as CD86 for all three cell types and a favorable ratio of interleukin (IL)‐12p40 to IL‐10 for monocytes stimulated with MSU + TDB. There was no significant production of IL‐12p40 by Mo‐DC; however, in a mixed lymphocyte assay, MSU + TDB costimulation of Mo‐DC led to a significant increase in CD4 + T‐cell numbers and in the IL‐12p40‐to‐IL‐10 ratio. Taken together, these findings show for the first time the potential of MSU + TDB costimulation to favor a tumor‐suppressive phenotype in human‐derived myeloid cells.