癌症疫苗的功效仍然较低，对癌症中抗原呈递细胞功能的机制了解可能会改善疫苗设计和结果。在这里，我们分析了参与晚期黑色素瘤 DC 疫苗试验的 35 名受试者的树突状细胞 (DC) 的转录组学和免疫代谢特征 (NCT01622933)。多个平台将代谢确定为 DC 功能和患者总生存 (OS) 的重要生物标志物。我们证明了患者疫苗中多种免疫和代谢基因表达途径的改变、OCR/OXPHOS 的功能性降低以及 ECAR/糖酵解的增加。为了剖析分子机制，我们利用单细胞 SCENITH 功能分析并显示患者临床结果 (OS) 与 DC 代谢特征相关，并且代谢与免疫表型相关。通过单细胞代谢调节组分析，我们发现 MCT1（单羧酸转运蛋白-1）（一种乳酸转运蛋白）在患者 DC 中增加，葡萄糖摄取和乳酸分泌也增加。重要的是，用作 DC 疫苗生成前体的患者的接种前循环骨髓细胞在代谢上存在显着偏差，几个 DC 亚群也是如此。我们共同证明 DC 的代谢特征与癌症患者 DC 疫苗的免疫刺激潜力密切相关。我们将表型和功能代谢变化与与抑制 DC 分化相对应的免疫特征联系起来。© 2023。作者。

Efficacy of cancer vaccines remains low and mechanistic understanding of antigen presenting cell function in cancer may improve vaccine design and outcomes. Here, we analyze the transcriptomic and immune-metabolic profiles of Dendritic Cells (DCs) from 35 subjects enrolled in a trial of DC vaccines in late-stage melanoma (NCT01622933). Multiple platforms identify metabolism as an important biomarker of DC function and patient overall survival (OS). We demonstrate multiple immune and metabolic gene expression pathway alterations, a functional decrease in OCR/OXPHOS and increase in ECAR/glycolysis in patient vaccines. To dissect molecular mechanisms, we utilize single cell SCENITH functional profiling and show patient clinical outcomes (OS) correlate with DC metabolic profile, and that metabolism is linked to immune phenotype. With single cell metabolic regulome profiling, we show that MCT1 (monocarboxylate transporter-1), a lactate transporter, is increased in patient DCs, as is glucose uptake and lactate secretion. Importantly, pre-vaccination circulating myeloid cells in patients used as precursors for DC vaccine generation are significantly skewed metabolically as are several DC subsets. Together, we demonstrate that the metabolic profile of DC is tightly associated with the immunostimulatory potential of DC vaccines from cancer patients. We link phenotypic and functional metabolic changes to immune signatures that correspond to suppressed DC differentiation.© 2023. The Author(s).