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.

中文翻译：

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海藻糖二山hen酸酯和尿酸一钠晶体的共同给药可促进人源性髓样细胞的抗肿瘤表型

海藻糖二山hen酸酯（TDB）是巨噬细胞诱导型C型凝集素的配体，已显示出作为预防性疫苗的佐剂以及在鼠类试验中作为抗癌剂的希望。然而，尚未研究TDB影响人类骨髓细胞抗肿瘤免疫应答的潜力。我们研究了佐剂TDB和尿酸钠（MSU）晶体对人单核细胞，巨噬细胞和单核细胞衍生的树突状细胞（Mo-DCs）的肿瘤或抗肿瘤免疫表型的影响。单独的TDB治疗会导致所有三种细胞类型的炎症反应，这在使用人单核细胞时最为明显，而MSU会增强这种反应。TDB还减少了与致瘤表型相关的细胞表面标志物，MSU显示出增强这种反应的能力。值得注意的是 TDB或MSU + TDB处理后，所有抗原呈递细胞的CD115均显着减少。用TDB和MSU + TDB处理后，还观察到了增加髓样细胞抗原呈递能力的潜力，这表现为所有三种细胞类型的细胞表面标志物（例如CD86）上调和白介素（IL）的有利比例MSU + TDB刺激的单核细胞）-12p40至IL-10。Mo-DC没有大量产生IL-12p40。然而，在混合淋巴细胞测定中，Mo-DC的MSU + TDB共刺激导致CD4显着增加 如所有三种细胞类型的细胞表面标志物（例如CD86）上调以及MSU + TDB刺激的单核细胞的白介素（IL）-12p40与IL-10的有利比率所表明的那样。Mo-DC没有大量产生IL-12p40。然而，在混合淋巴细胞测定中，Mo-DC的MSU + TDB共刺激导致CD4显着增加 如所有三种细胞类型的细胞表面标志物（例如CD86）的上调所指示，以及MSU + TDB刺激的单核细胞的白介素（IL）-12p40与IL-10的有利比例。Mo-DC没有大量产生IL-12p40。然而，在混合淋巴细胞测定中，Mo-DC的MSU + TDB共刺激导致CD4显着增加⁺ T细胞编号以及IL-12p40与IL-10的比率。综上所述，这些发现首次显示了MSU + TDB共刺激在人源性髓样细胞中支持肿瘤抑制表型的潜力。