在头颈鳞状细胞癌 (HNSCC) 的背景下，树突状细胞 (DC) 承担着关键的职责，充当抗原呈递的设计师和免疫检查点调节的指挥者。在这项研究中，我们旨在鉴定与 HNSCC 中 DC 相关的中心基因，并探讨其预后意义和对免疫治疗的影响。来自癌症基因组图谱 (TCGA)-HNSCC 和 GSE65858 队列的综合临床数据集经过了细致的分析。采用加权基因共表达网络分析（WGCNA），我们描绘了与 DC 相关的候选基因。通过应用随机生存森林和最小绝对收缩和选择算子（LASSO）Cox回归，我们得出了重要的关键基因。 Lisa（表观遗传景观计算机删除分析和 MARGE 的第二个后代）强调了转录因子，双荧光素酶测定证实了它们的调节作用。此外，利用肿瘤免疫功能障碍和排除在线工具评估免疫治疗敏感性。这项研究阐明了 HNSCC DC 亚群的功能复杂性，以定制创新的治疗策略。我们利用了 TCGA-HNSCC 和 GSE65858 队列的临床数据。我们对数据进行了高级分析，包括 WGCNA，它揭示了 222 个与 DC 相关的候选基因。此后，利用随机生存森林分析和 LASSO Cox 回归的辨别方法揭示了与 DC 预后影响相关的 7 个基因，特别是 ACP2 和 CPVL，它们与较差的总体生存率相关。 ACP2和ACP2-DC细胞之间的差异基因表达分析揭示了208个差异表达基因。 Lisa 分析确定了前 5 个重要的转录因子：STAT1、SPI1、SMAD1、CEBPB 和 IRF1。通过 HEK293T 细胞中的定量逆转录聚合酶链反应 (qRT-PCR) 和双荧光素酶测定证实了 STAT1 和 ACP2 之间的相关性。此外，TP53 和 FAT1 突变在高风险 DC 亚组中更为常见。重要的是，不同风险群对免疫治疗的敏感性不同。预计低风险人群对免疫治疗表现出良好的反应，其特点是免疫系统相关标记物的表达升高。相比之下，高风险组的免疫抑制细胞比例增加，这表明免疫治疗干预的环境不太有利。我们的研究可能会产生一个基于 DC 的 HNSCC 预后系统。随着与这种具有挑战性的癌症的斗争继续进行，这将有助于个性化治疗并改善临床结果。2024 转化癌症研究。版权所有。

In the context of head-and-neck squamous cell carcinoma (HNSCC), dendritic cells (DCs) assume pivotal responsibilities, acting as architects of antigen presentation and conductors of immune checkpoint modulation. In this study, we aimed to identify hub genes associated with DCs in HNSCC and explore their prognostic significance and implications for immunotherapy.Integrated clinical datasets from The Cancer Genome Atlas (TCGA)-HNSCC and GSE65858 cohorts underwent meticulous analysis. Employing weighted gene co-expression network analysis (WGCNA), we delineated candidate genes pertinent to DCs. Through the application of random survival forest and least absolute shrinkage and selection operator (LASSO) Cox's regression, we derived key genes of significance. Lisa (epigenetic Landscape In Silico deletion Analysis and the second descendent of MARGE) highlighted transcription factors, with Dual-luciferase assays confirming their regulatory role. Furthermore, immunotherapeutic sensitivity was assessed utilizing the Tumor Immune Dysfunction and Exclusion online tool.This study illuminated the functional intricacies of HNSCC DC subsets to tailor innovative therapeutic strategies. We leveraged clinical data from the TCGA-HNSCC and GSE65858 cohorts. We subjected the data to advanced analysis, including WGCNA, which revealed 222 DC-related candidate genes. Following this, a discerning approach utilizing random survival forest analysis and LASSO Cox's regression unveiled seven genes associated with the prognostic impact of DCs, notably ACP2 and CPVL, associated with poor overall survival. Differential gene expression analysis between ACP2 + and ACP2 - DC cells revealed 208 differential expressed genes. Lisa analysis identified the top five significant transcription factors as STAT1, SPI1, SMAD1, CEBPB, and IRF1. The correlation between STAT1 and ACP2 was confirmed through quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Dual-luciferase assays in HEK293T cells. Additionally, TP53 and FAT1 mutations were more common in high-risk DC subgroups. Importantly, the sensitivity to immunotherapy differed among the risk clusters. The low-risk cohorts were anticipated to exhibit favorable responses to immunotherapy, marked by heightened expressions of immune system-related markers. In contrast, the high-risk group displayed augmented proportions of immunosuppressive cells, suggesting a less conducive environment for immunotherapeutic interventions.Our research may yield a robust DC-based prognostic system for HNSCC; this will aid personalized treatment and improve clinical outcomes as the battle against this challenging cancer continues.2024 Translational Cancer Research. All rights reserved.