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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

^ 18F-FDG-PET 预测口腔鳞状细胞癌肿瘤 PD-L1 和 CD8 ^ + 肿瘤浸润淋巴细胞肿瘤免疫状态的诊断价值

  • 影响因子:5.52
  • DOI:10.1038/s41416-020-0820-z
  • 作者列表:"Togo, Maria","Yokobori, Takehiko","Shimizu, Kimihiro","Handa, Tadashi","Kaira, Kyoichi","Sano, Takaaki","Tsukagoshi, Mariko","Higuchi, Tetsuya","Yokoo, Satoshi","Shirabe, Ken","Oyama, Tetsunari
  • 发表时间:2020-04-02
Abstract

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, ^18F-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 ^18F-FDG-uptake, clinicopathological characteristics and prognosis. Results Low expression of PD-L1 in OSCC correlated with cancer aggressiveness, poor prognosis, high ^18F-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 ^18F-FDG-uptake and E-cadherin suppression. Furthermore, the high level of preoperative ^18F-FDG-uptake in OSCC was an independent predictor of the cold tumour immune status. Conclusions ^18F-FDG-uptake is an independent predictor of cold tumour in OSCC. ^18F-FDG-PET imaging could be a promising diagnostic tool to estimate tumour immune status.

摘要

背景: 最近,免疫检查点蛋白,如程序性死亡 1 (PD-1) 及其 ligand-1 (PD-L1),作为一个新的靶点在口腔鳞状细胞癌 (OSCC) 中受到关注。据报道,通过 anti-PD-1 抗体治疗的氟-d-葡萄糖 (FDG) 摄取改变描述了肺癌患者的反应。本研究旨在探讨 OSCC 中肿瘤免疫状态、临床病理因素、 ^ 18f-fdg 摄取与 PD-L1 低表达/低 CD8 ^ + 肿瘤浸润淋巴细胞 (til) 的关系。方法对 59 例手术切除的 OSCC 标本进行 PD-L1 、缺氧诱导因子 1 a (HIF-1A) 、葡萄糖转运蛋白 1 (GLUT1) 、 CD8 、 E-cadherin 和 Ki-67 的免疫组化分析。我们评估了这些因素与术前 ^ 18f-fdg 摄取、临床病理特征和预后之间的相关性。结果 OSCC 中 PD-L1 低表达与肿瘤侵袭性、不良预后、高 ^ 18f-fdg 摄取 (HIF-1A/GLUT1) 、低 E-cadherin 表达和低 cd8 相关。低 PD-L1 肿瘤细胞和低间质 CD8 与预后不良、高 ^ 18f-fdg-摄取和 E-cadherin 抑制相关。此外,OSCC 术前 ^ 18f-fdg-摄取水平高是冷肿瘤免疫状态的独立预测因子。结论 ^ 18f-fdg 摄取是 OSCC 冷肿瘤的独立预测因子。^ 18F-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。

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