Role of PD-L1 Expression during the Progression of Submucosal Gastric Cancer
Role of PD-L1 Expression during the Progression of Submucosal Gastric Cancer
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DOI：
10.1159/000509033
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发表时间：
2021-01-01
期刊：
影响因子：
3.5
通讯作者：
Saeki, Hiroshi
中科院分区：
文献类型：
--
作者：
Ubukata, Yasunari;Ogata, Kyoichi;Saeki, Hiroshi
简介：程序性死亡配体1（PD-L1）表达是胃癌的预后标志物，与肿瘤直径和穿透深度相关。但PD-L1在早期胃癌侵袭初始阶段的作用及其机制尚不清楚。目的：本研究旨在阐明PD-L1在胃癌进展过程中的作用，特别是浸润粘膜肌层以外的粘膜下层。研究方法：使用107例病理性粘膜下胃癌患者，我们基于肿瘤中央和浸润前沿的肿瘤细胞的细胞膜或细胞质的染色来确定PD-L1的表达。根据PD-L1表达强度将样本分为3组。使用表达PD-1的CD 8（+）淋巴细胞和CD 163（+）巨噬细胞来确定浸润前沿的细胞核数量，类似于PD-L1。测定CMTM 6水平并用于将样品分层为3组。结果：PD-L1在浸润前沿的表达（26.2%）高于肿瘤中心部分（7.4%; p < 0.001）。此外，在具有高水平PD-L1的样本中更频繁地观察到淋巴和血管浸润（淋巴浸润：60.7 vs. 35.4%，p = 0.0026，血管浸润：39.3 vs. 16.5%，p = 0.0018）。PD-L1表达与PD-1、CD 8、CD 163和CMTM 6水平之间无相关性。结论：胃癌浸润前沿的PD-L1表达癌细胞影响早期胃癌中肿瘤浸润和淋巴血管渗透的初始阶段。免疫检查点信号传导可能是粘膜肌层以外的粘膜下层浸润过程中浸润前沿的驱动力。
Introduction: Programmed death-ligand 1 (PD-L1) expression is a prognostic marker for gastric cancer that correlates with tumor diameter and depth of penetration. But the role of PD-L1 and mechanism(s) employed in the initial phase of invasion in early gastric cancer is yet to be understood. Objective: This study aims to elucidate the role of PD-L1 during the progression of gastric cancer, specifically invading the submucosa beyond the lamina muscularis mucosa. Methods: Using 107 patients with pathological submucosal gastric cancer, we determined the expression of PD-L1 based on the staining of the cell membrane or cytoplasm of tumor cells in the central and invasive front of the tumor. Samples were categorized into 3 groups based on the intensity of PD-L1 expression. CD8(+) lymphocytes expressing PD-1 and CD163(+) macrophages were used to determine the number of cell nuclei at the invasive front, similar to PD-L1. CMTM6 levels were determined and used to stratify samples into 3 groups. Results: PD-L1 expression was higher in the invasive front (26.2%) than in the central portion of the tumors (7.4%; p < 0.001). Moreover, lymphatic and vascular invasion were more frequently observed in samples with high levels of PD-L1 (lymphatic invasion: 60.7 vs. 35.4%, p = 0.0026, and vascular invasion: 39.3 vs. 16.5%, p = 0.0018). There was no correlation between PD-L1 expression and the levels of PD-1, CD8, CD163, and CMTM6. Conclusions: PD-L1-expressing cancer cells at the invasive front of gastric cancer influence the initial stages of tumor invasion and lymphovascular permeation in early-stage gastric cancers. Immune checkpoint signaling may be the driving force in the invasive front during the invasion of the submucosa beyond the lamina muscularis mucosa.