Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute; MOE Key Laboratory of Major Diseases in Children; Rare Disease Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Oncoimmunology. 2023 Apr 18;12(1):2203073. doi: 10.1080/2162402X.2023.2203073. eCollection 2023.
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 () expression are associated with more aggressive and metastatic characteristics in multiple cancers. However, the link between the 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 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 and on macrophages. A total of 498 tumor samples of HNSCC patients from The Cancer Genome Atlas (TCGA) database were also analyzed. Remarkably, expression was dramatically higher in HNSCC tissues than that in adjacent normal tissues, and the patients with high levels of expression had significantly unfavorable overall survival (Hazard Ratio = 1.724, log-rank -value = 0.0066) when compared to patients harboring low expression levels of . In summary, we reported that the specific expression of on the TAMs was significantly correlated with poor survival outcomes, revealing that could serve as a potential prognosis marker and promising target for immunotherapy in HNSCC.
头颈部鳞状细胞癌（HNSCC）是免疫浸润程度最高的人类肿瘤之一，具有与不同分子特征和临床结果相关的独特免疫亚型。HNSCC 的肿瘤微环境（TME）主要由肿瘤相关巨噬细胞（TAMs）组成，预后相对较差。氧化型低密度脂蛋白受体 1（）的高表达与多种癌症中更具侵袭性和转移性的特征有关。然而，表达与 TME 免疫抑制之间的联系，以及控制肿瘤内 TAMs 行为的分子机制尚不清楚。在这里，我们基于 HNSCC 的单细胞 RNA-seq（scRNA-seq）数据集进行了转录分析，发现表达特异性富集在 TAMs 上。对原发性 HNSCC 患者样本组织学切片中蛋白表达的评估表明，和在巨噬细胞上存在共表达模式。总共分析了来自癌症基因组图谱（TCGA）数据库的 498 例 HNSCC 患者的肿瘤样本。值得注意的是，与相邻正常组织相比，HNSCC 组织中表达显著升高，与表达水平低的患者相比，表达水平高的患者的总生存率明显不利（风险比=1.724，对数秩检验值=0.0066）。总之，我们报道了 TAMs 上的特异性表达与不良生存结局显著相关，表明可能成为 HNSCC 免疫治疗的潜在预后标志物和有前途的靶标。
