头颈鳞状细胞癌（HNSCC）是免疫浸润最重的人类肿瘤之一，具有不同分子特征和临床结果相关的不同免疫亚型。由肿瘤相关巨噬细胞（TAMs）主导的HNSCC肿瘤微环境（TME）具有相对较差的预后。氧化低密度脂蛋白受体1（OLR1）的高表达水平与多种癌症的更具侵袭性和转移性特征相关。然而，OLR1表达与TME的免疫抑制之间的联系以及控制肿瘤内TAM行为的分子机制仍不清楚。在此，我们基于头颈鳞状细胞癌的单细胞RNA测序（scRNA-seq）数据集进行转录分析，并发现OLR1表达特别富集在TAMs上。评估原发性HNSCC患者样本的组织切片中的蛋白表达显示，OLR1和CD68在巨噬细胞上具有共表达模式。我们还分析了The Cancer Genome Atlas（TCGA）数据库中498例HNSCC患者的肿瘤样本。值得注意的是，HNSCC组织中OLR1表达显著高于相邻正常组织，而OLR1表达水平高的患者相比于低表达水平的患者有明显不利的总体生存率（风险比=1.724，对数秩和P值=0.0066）。总之，我们报告了OLR1特异性表达于TAM上，与不良生存结果显著相关，揭示了OLR1可能作为头颈鳞状细胞癌免疫治疗潜在的预后标志和有希望的靶点。© 2023作者。在Taylor＆Francis Group，LLC授权下发表。

Head and neck squamous cell carcinoma (HNSCC) is one of the most heavily immune infiltrated human tumors, having distinct immune subtypes associated with different molecular characteristics and clinical outcomes. The tumor microenvironment (TME) of HNSCC which was dominated by tumor-associated macrophages (TAMs) had a relatively inferior prognosis. High levels of oxidized low-density lipoprotein receptor 1 (OLR1) expression are associated with more aggressive and metastatic characteristics in multiple cancers. However, the link between the OLR1 expression and immunosuppression of TME, and the molecular mechanisms which govern intratumoral TAMs behavior are unclear. Here, we performed the transcriptional analysis based on a single-cell RNA-sequencing (scRNA-seq) dataset of HNSCC, and found that the OLR1 expression was specifically enriched on the TAMs. Evaluation of protein expression within histologic sections of primary HNSCC patient samples showed a co-expression pattern of OLR1 and CD68 on macrophages. A total of 498 tumor samples of HNSCC patients from The Cancer Genome Atlas (TCGA) database were also analyzed. Remarkably, OLR1 expression was dramatically higher in HNSCC tissues than that in adjacent normal tissues, and the patients with high levels of OLR1 expression had significantly unfavorable overall survival (Hazard Ratio = 1.724, log-rank P-value = 0.0066) when compared to patients harboring low expression levels of OLR1. In summary, we reported that the specific expression of OLR1 on the TAMs was significantly correlated with poor survival outcomes, revealing that OLR1 could serve as a potential prognosis marker and promising target for immunotherapy in HNSCC.© 2023 The Author(s). Published with license by Taylor & Francis Group, LLC.