BACKGROUND Metabolic information obtained through 18F-flurodeoxyglucose positron emission tomography/computed tomography (18F-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 18F-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 18F-FDG PET/CT could be a potential predictor for selecting candidates for immunotherapy.

中文翻译：

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非小细胞肺癌患者18F-FDG PET / CT代谢状态与免疫标志物表达相关性的新见解。

背景技术通过18F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（18F-FDG PET / CT）获得的代谢信息用于通过计算葡萄糖摄取率来评估恶性肿瘤，这些参数在确定非小细胞肺癌的预后中起着重要作用。癌症（NSCLC）。肿瘤组织中免疫相关标志物的表达反映了肿瘤微环境中的免疫状态。然而，缺乏关于代谢变量与肿瘤内免疫标志物之间关联的报道。在本文中，我们调查了18F-FDG PET / CT的代谢状态与NSCLC患者肿瘤内免疫标志物表达之间的相关性。方法从2008年4月至2014年8月，该研究纳入了763名患者，以研究最大标准化摄取值（SUVmax）在肺癌中的作用。通过免疫组织化学（IHC）分析了122个肿瘤标本对肿瘤内免疫细胞和肿瘤细胞上程序性死亡蛋白配体1（PD-L1）的表达。分析了代谢变量与组织免疫标志物表达之间的相关性。结果SUVmax值在不同的表皮生长因子受体（EGFR）状态（野生型与突变型），中性粒细胞与淋巴细胞比（NLR）组高/低以及血小板与淋巴细胞比（PLR）高/低之间具有显着差异。 ）组（分别为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）。IHC显示SUVmax与CD8肿瘤浸润淋巴细胞（p = 0.015），CD163肿瘤相关巨噬细胞（TAM）（p = 0.003）和Foxp3调节性T细胞（Tregs）的表达之间具有统计学意义的相关性（p = 0.004 ），PD-1和PD-L1（分别为p = 0.003和p = 0.012）。在患者预后方面，疾病阶段，BMI，SUVmax，代谢肿瘤体积（MTV），TLG（肿瘤病变糖酵解），CD163-TAM，CD11c树突状细胞（DC），PD-L1和Treg显示出统计学显着的相关性无进展生存期（PFS）（分别为p <0.001、0.023，<0.001、0.007、0.005、0.004、0.008、0.048和0.014），以及疾病阶段，SUVmax，MTV，TLG，CD163-TAM，CD11c- DC和PD-L1与总体生存率（OS）在统计上具有显着相关性（p <0.001，<0.001、0.014、0.012，分别<0.001、0.001和<0.001）。结论这项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联，并表明18F-FDG PET / CT上的SUVmax可能是选择免疫疗法候选者的潜在预测指标。