Department of General Surgery, Graduate School of Medical Sciences, Gunma University, Maebashi, Japan.
Department of General Surgery, Graduate School of Medical Sciences, Gunma University, Maebashi, Japan,
Oncology. 2021;99(1):15-22. doi: 10.1159/000509033. Epub 2020 Oct 28.
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.
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.
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.
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.
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.
程序性死亡配体 1（PD-L1）的表达是胃癌的一种预后标志物，与肿瘤直径和浸润深度相关。但是，PD-L1在早期胃癌浸润的初始阶段的作用及其机制尚不清楚。
本研究旨在阐明 PD-L1 在胃癌进展过程中的作用，特别是在黏膜下层侵犯黏膜肌层以外的阶段。
使用 107 例有病理黏膜下胃癌的患者，我们根据肿瘤细胞的细胞膜或细胞质染色，确定 PD-L1 在肿瘤中央和浸润前缘的表达。根据 PD-L1 表达强度将样本分为 3 组。用 PD-1 和 CD163+巨噬细胞表达的 CD8+淋巴细胞来确定浸润前缘的细胞核数量，类似于 PD-L1。测定 CMTM6 水平，并将样本分为 3 组。
PD-L1 在浸润前缘的表达（26.2%）高于肿瘤中央部分（7.4%；p<0.001）。此外，高 PD-L1 水平的样本中更频繁地观察到淋巴管和血管侵犯（淋巴管侵犯：60.7%比 35.4%，p=0.0026，血管侵犯：39.3%比 16.5%，p=0.0018）。PD-L1 表达与 PD-1、CD8、CD163 和 CMTM6 的水平之间没有相关性。
在胃癌浸润前缘表达 PD-L1 的癌细胞影响早期胃癌肿瘤浸润和淋巴血管渗透的初始阶段。免疫检查点信号可能是黏膜肌层以外的黏膜下层浸润过程中浸润前缘的驱动力。
