New insight on the correlation of metabolic status on 18F-FDG PET/CT with immune marker expression in patients with non-small cell lung cancer
New insight on the correlation of metabolic status on 18F-FDG PET/CT with immune marker expression in patients with non-small cell lung cancer
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非小细胞肺癌患者18F - 氟代脱氧葡萄糖正电子发射断层显像/计算机断层扫描（18F - FDG PET/CT）代谢状态与免疫标志物表达相关性的新见解
DOI：
10.1007/s00259-019-04500-7
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发表时间：
2020-05-01
影响因子：
9.1
通讯作者：
Ren, Xiubao
中科院分区：
文献类型：
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作者：
Wang, Yang;Zhao, Ning;Ren, Xiubao
背景通过F-18-脱氧葡萄糖正电子发射断层扫描/计算机断层扫描(F-18-FDG PET/CT)获得的代谢信息，通过计算葡萄糖摄取率来评估恶性程度，这些参数在判断非小细胞肺癌(NSCLC)的预后中起着重要作用。免疫相关标志物在肿瘤组织中的表达反映了肿瘤微环境中的免疫状态。然而，关于代谢变量和肿瘤内免疫标记物之间的关系的报道很少。在此，我们研究了非小细胞肺癌患者F-18-FDG PET/CT代谢状态与肿瘤内免疫标记物表达的相关性。方法对2008年4月至2014年8月收治的763例肺癌患者进行分析，探讨最大标准摄取值(SUVmax)在肺癌中的作用。对122例肿瘤标本进行瘤内免疫细胞免疫组化和肿瘤细胞程序性死亡蛋白配体1(PD-L1)的免疫组织化学分析。分析代谢变量与组织免疫标记物表达的相关性。结果不同状态的表皮生长因子受体(野生型与变异型)、高/低中性粒细胞/淋巴细胞比、高/低血小板/淋巴细胞比组的SUVmax值有显著差异(P<0.001，P<0.001，P=0.003)。SUVmax是肺癌患者的独立预后因素(p=0.013)。免疫组化显示SUVmax与CD8肿瘤浸润性淋巴细胞(p=0.015)、CD163肿瘤相关巨噬细胞(TAMs)(p=0.003)和Foxp3调节性T细胞(Tregs)(p=0.004)以及PD-1和PD-L1的表达(分别为p=0.003和p=0.012)显著相关。就患者预后、疾病分期、体重指数、最大尿流率、代谢性肿瘤体积、肿瘤病变糖酵解、CD163TAMS、CD11c树突状细胞(DC)、PD-L1和Tregs与无进展生存期(PFS)有统计学意义的相关性(p<；0.001、0.023和lt；疾病分期、SUVmax、MTV、TLG、CD163-TAMS、CD11c-DC和PD-L1与总生存期(OS)显著相关(P<；0.001、0.001、0.014、0.012、P<；0001、0001和P<0001)。结论本研究揭示了肿瘤微环境中代谢变量与免疫细胞表达之间的关系，提示F-18-FDG PET/CT的SUVmax可作为选择免疫治疗候选者的潜在预测指标。
Background Metabolic information obtained through F-18-flurodeoxyglucose positron emission tomography/computed tomography (F-18-FDG PET/CT) is used to evaluate malignancy by calculating the glucose uptake rate, and these parameters play important roles in determining the prognosis of non-small cell lung cancer (NSCLC). The expression of immune-related markers in tumor tissue reflects the immune status in the tumor microenvironment. However, there is lack of reports on the association between metabolic variables and intra-tumor immune markers. Herein, we investigate the correlation between metabolic status on F-18-FDG PET/CT and intra-tumor immunomarkers' expression in NSCLC patients. Methods From April 2008 to August 2014, 763 patients were enrolled in the analysis to investigate the role of maximum standardized uptake value (SUVmax) in lung cancer. One hundred twenty-two tumor specimens were analyzed by immunohistochemistry (IHC) to intra-tumor immune cells and programmed death protein ligand 1(PD-L1) expression on tumor cells. The correlation between metabolic variables and the expression of tissue immune markers were analyzed. Results SUVmax values have significant variations in different epidermal growth factor receptor (EGFR) statuses (wild type vs mutant type), high/low neutrophil-to-lymphocyte ratio (NLR) groups, and high/low platelets-to-lymphocyte ratio (PLR) groups (p < 0.001, p < 0.001, p = 0.003, respectively). SUVmax was an independent prognostic factor in lung cancer patients (p = 0.013). IHC demonstrated a statistically significant correlation between SUVmax and the expression of CD8 tumor-infiltrating lymphocytes (p = 0.015), CD163 tumor-associated macrophages (TAMs) (p = 0.003), and Foxp3-regulatory T cells (Tregs) (p = 0.004), as well as PD-1 and PD-L1 (p = 0.003 and p = 0.012, respectively). With respect to patient outcomes, disease stage, BMI, SUVmax, metabolic tumor volume (MTV), TLG (tumor lesion glycolysis), CD163-TAMs, CD11c-dendritic cells (DCs), PD-L1, and Tregs showed a statistically significant correlation with progression-free survival (PFS) (p < 0.001, 0.023, < 0.001, 0.007, 0.005, 0.004, 0.008, 0.048, and 0.014, respectively), and disease stage, SUVmax, MTV, TLG, CD163-TAMs, CD11c-DCs, and PD-L1 showed a statistically significant correlation with overall survival (OS) (p < 0.001, < 0.001, 0.014, 0.012, < 0.001, 0.001, and < 0.001, respectively). Conclusion This study revealed an association between metabolic variable and immune cell expression in the tumor microenvironment and suggests that SUVmax on F-18-FDG PET/CT could be a potential predictor for selecting candidates for immunotherapy.