Diagnostic value of 18F-FDG-PET to predict the tumour immune status defined by tumoural PD-L1 and CD8+tumour-infiltrating lymphocytes in oral squamous cell carcinoma
Diagnostic value of 18F-FDG-PET to predict the tumour immune status defined by tumoural PD-L1 and CD8+tumour-infiltrating lymphocytes in oral squamous cell carcinoma
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DOI：
10.1038/s41416-020-0820-z
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发表时间：
2020-04-02
影响因子：
8.8
通讯作者：
Oyama, Tetsunari
中科院分区：
文献类型：
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作者：
Togo, Maria;Yokobori, Takehiko;Oyama, Tetsunari
背景 最近，免疫检查点蛋白，如程序性死亡 1 (PD-1) 及其配体 1 (PD-L1)，作为口腔鳞状细胞癌 (OSCC) 的新靶点引起了人们的关注。据报道，抗 PD-1 抗体治疗对氟代葡萄糖 (FDG) 摄取的改变反映了肺癌患者的反应。本研究旨在阐明 OSCC 中肿瘤免疫状态、临床病理因素、F-18-FDG 摄取与低 PD-L1 表达/低 CD8(+) 肿瘤浸润淋巴细胞 (TIL) 冷肿瘤表型之间的相关性。方法 我们对 59 个可手术 OSCC 样本进行 PD-L1、缺氧诱导因子 1 A (HIF-1A)、葡萄糖转运蛋白 1 (GLUT1)、CD8、E-钙粘蛋白和 Ki-67 的免疫组织化学分析。我们评估了这些因素与术前 F-18-FDG 摄取、临床病理特征和预后之间的相关性。结果 OSCC 中 PD-L1 的低表达与癌症侵袭性、不良预后、HIF-1A/GLUT1 的高 F-18-FDG 摄取以及低 E-cadherin 表达和低 CD8 相关。冷肿瘤表型如低 PD-L1 肿瘤细胞和低基质 CD8 与不良预后、高 F-18-FDG 摄取和 E-钙粘蛋白抑制相关。此外，OSCC术前高水平的F-18-FDG摄取是冷肿瘤免疫状态的独立预测因子。结论 F-18-FDG 摄取是 OSCC 冷肿瘤的独立预测因子。 F-18-FDG-PET 成像可能是估计肿瘤免疫状态的一种有前途的诊断工具。
Background Lately, immune checkpoint proteins, such as programmed death 1 (PD-1) and its ligand-1 (PD-L1), have garnered attention as a new target in oral squamous cell carcinoma (OSCC). Reportedly, fluoro-d-glucose (FDG)-uptake alteration by anti-PD-1 antibody treatment depicts the response in patients with lung cancer. This study aims to elucidate the correlations between tumour immune status, clinicopathological factors, F-18-FDG-uptake and cold tumour phenotypes as low PD-L1 expression/low CD8(+)tumour-infiltrating lymphocytes (TILs) in OSCC. Methods We performed immunohistochemical analysis of PD-L1, hypoxia-inducible factor 1 A (HIF-1A), glucose transporter type 1 (GLUT1), CD8, E-cadherin and Ki-67 on 59 operable OSCC samples. We assessed the correlations between these factors and preoperative F-18-FDG-uptake, clinicopathological characteristics and prognosis. Results Low expression of PD-L1 in OSCC correlated with cancer aggressiveness, poor prognosis, high F-18-FDG-uptake with HIF-1A/GLUT1 and low E-cadherin expression and low CD8. Cold tumour phenotypes as low PD-L1 tumour cells and low stromal CD8 correlated with the poor prognosis, high F-18-FDG-uptake and E-cadherin suppression. Furthermore, the high level of preoperative F-18-FDG-uptake in OSCC was an independent predictor of the cold tumour immune status. Conclusions F-18-FDG-uptake is an independent predictor of cold tumour in OSCC. F-18-FDG-PET imaging could be a promising diagnostic tool to estimate tumour immune status.