关键词: CAFs Oral squamous cell carcinoma PD-L1 p53 α-SMA

来  源:   DOI:10.1186/s40902-024-00441-w   PDF(Pubmed)

Abstract:
BACKGROUND: Tumor tissues comprise cancer cells and stromal cells, and their interactions form the cancer microenvironment. Therefore, treatments targeting cells other than cancer cells are also actively being developed, and among them, treatment targeting PD-1, an immune checkpoint molecule that is important in tumor immune evasion, has also been indicated for head and neck cancer. PD-L1, a ligand of PD-1, is expressed in both tumor cells and stromal cells, and the scoring system based on the combined positivity rates of both types of cells, the combined positive score (CPS), is used for predicting treatment effect. However, much is unknown regarding the expression of PD-L1. In this study, we histopathologically examined factors controlling the expression of PD-1/PD-L1. This study included 37 patients who underwent resection surgery for tongue squamous cell carcinoma in the Department of Oral and Maxillofacial Surgery at Tokyo Dental College Suidobashi Hospital. The expression levels of PD-L1, α-SMA, and p53 were assessed by immunohistochemical staining.
RESULTS: Seven participants had CPS ≥ 20, twenty-four participants had 1 ≤ CPS < 20, and six participants had CPS < 1. The overall positivity rate of α-SMA, a marker for cancer-associated fibroblasts (CAFs), was 27% (10/37 participants), and the positivity rates of α-SMA for the three CPS groups were 85.7% (6/7 participants), 16.7% (4/24 participants), and 0% (0/6 participants), respectively. In addition, the overall positivity rate of p53 was 37.8% (14/37 participants), and the positivity rates of p53 for the three CPS groups were 71.4% (5/7 participants), 37.5% (9/24 participants), and 0% (0/6 participants), respectively.
CONCLUSIONS: The expression of PD-L1 demonstrated an association with α-SMA and p53 positivity. In addition, compared with the expression of p53, the expression of α-SMA demonstrated a higher association with PD-L1 expression in patients with a high CPS. The abovementioned findings suggest that the interactions between CAFs, cancer cells, and immunocompetent cells may regulate the expression of PD-L1.
摘要:
背景:肿瘤组织包括癌细胞和基质细胞,它们的相互作用形成了癌症微环境。因此,针对癌细胞以外的细胞的治疗也正在积极开发中,其中,针对PD-1的治疗,PD-1是一种在肿瘤免疫逃避中很重要的免疫检查点分子,也适用于头颈部癌症。PD-L1是PD-1的配体,在肿瘤细胞和基质细胞中均有表达,以及基于两种类型细胞的综合阳性率的评分系统,综合阳性评分(CPS),用于预测治疗效果。然而,关于PD-L1的表达尚不清楚。在这项研究中,我们通过组织病理学检查了控制PD-1/PD-L1表达的因素。这项研究包括在东京牙科学院Suidobashi医院口腔颌面外科接受舌鳞状细胞癌切除手术的37例患者。PD-L1、α-SMA的表达水平,通过免疫组织化学染色评估p53。
结果:7名参与者CPS≥20,24名参与者1≤CPS<20,6名参与者CPS<1。α-SMA的总体阳性率,癌症相关成纤维细胞(CAFs)的标志物,27%(10/37名参与者),三个CPS组的α-SMA阳性率为85.7%(6/7),16.7%(4/24参与者),和0%(0/6参与者),分别。此外,p53的总体阳性率为37.8%(14/37),三个CPS组的p53阳性率为71.4%(5/7),37.5%(9/24参与者),和0%(0/6参与者),分别。
结论:PD-L1的表达与α-SMA和p53阳性相关。此外,与p53的表达相比,α-SMA的表达与高CPS患者的PD-L1表达有更高的相关性。上述研究结果表明,CAF之间的相互作用,癌细胞,免疫活性细胞可以调节PD-L1的表达。
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