Fluorodeoxyglucose uptake is associated with low tumor-infiltrating lymphocyte levels in patients with small cell lung cancer
Fluorodeoxyglucose uptake is associated with low tumor-infiltrating lymphocyte levels in patients with small cell lung cancer
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DOI：
10.1016/j.lungcan.2019.06.009
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发表时间：
2019-08-01
期刊：
影响因子：
5.3
通讯作者：
Hisada, Takeshi
中科院分区：
文献类型：
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作者：
Kasahara, Norimitsu;Kaira, Kyoichi;Hisada, Takeshi
目的：2-脱氧-2-[F-18]氟-D-葡萄糖(F-18-FDG)正电子发射断层扫描(PET)是一种临床上有用的肿瘤评估方法。肿瘤细胞摄取F-18-FDG的机制涉及葡萄糖转运蛋白1(GLUT1)和缺氧诱导因子-1α(HIF-1α)。虽然最近的研究表明它在小细胞肺癌(SCLC)中的临床疗效，但还没有确定合适的生物标志物。材料和方法：采用免疫组织化学方法检测肿瘤组织中GLUT1、HIF-1α、PD-L1、CD4、CD8和Foxp3的表达。分析临床病理特征与F-18-FDG摄取的关系。采用学生t检验、X(2)检验、非参数Spearman等级检验和Kaplan-Meier方法对各变量之间的相关性进行评估。结果：共98例患者接受了F-18-FDG PET检查，男78例，女20例。PD-L1阳性率为36.7%(36/98)，与GLUT1表达显著相关(p=0.04)。CD8和CD4TIL低的患者F-18-FDG积聚显著高于TIL高的患者(分别为p=0.03和p=0.01)。摄取F-18-FDG与Foxp3或PD-L1的表达均无显著相关性。多因素分析显示，晚期、ECOG-PS差和高SUVmax是OS差的独立预测因素。在局限期疾病患者中，多因素分析证实PD-L1高表达和高SUVmax是不良OS的独立预测因素。然而，在广泛分期的肿瘤患者中，仅ECOG-PS被发现是OS不良的独立预测因素。结论：F-18-FDG-PET的高SUVmax与CD8(+)和CD4(+)TIL的低表达相关，但可作为OS的独立预后因素，尤其是在疾病有限的患者。有必要进行进一步的研究来验证我们的发现。
Objectives: Positron emission tomography (PET) using 2-deoxy-2-[F-18] fluoro-D-glucose (F-18-FDG) is a clinically useful modality for cancer evaluation. The mechanism of F-18-FDG uptake within cancer cells involves the glucose transporter 1 (GLUT1) and hypoxia-inducible factor-1 alpha (HIF-1 alpha). Although recent research has shown its clinical efficacy in small-cell lung cancer (SCLC), no suitable biomarker has been identified. We conducted a clinicopathological study to examine the relationship between tumor immunity and F-18-FDG uptake in patients with SCLC.Materials and methods: Tumor sections were stained by immunohistochemistry for GLUT1, HIF-1 alpha, PD-L1, CD4, CD8, and Foxp3. The relationship between clinicopathological features and F-18-FDG uptake was analyzed. Student's t-test, chi(2) test, non-parametric Spearman's rank test, and Kaplan-Meier method were used to evaluate associations between the variables.Results: A total of 98 patients 78 men and 20 women who underwent F-18-FDG PET, were enrolled in this study. PD-L1 was expressed in 36.7% (36/98) of all patients; this was significantly associated with GLUT1 expression (p = 0.04). The accumulation of F-18-FDG was significantly higher in patients with low CD8 and CD4 TILs than in those with high TILs (p = 0.03 and p = 0.01, respectively). The uptake of F-18-FDG was not significantly associated with the expression of either Foxp3 or PD-L1. Multivariate analysis demonstrated that advanced stage, poor ECOG-PS, and high SUVmax were independent predictors of poor OS. Among patients with limited-stage disease, multivariate analysis confirmed high PD-L1 expression and a high SUVmax to be independent predictors of poor OS. However, only ECOG-PS was found to be an independent predictor of poor OS among patients with extensive-stage tumors.Conclusion: High SUVmax on F-18-FDG-PET is correlated with low expression of CD8(+) and CD4(+) TILs, but is an independent prognostic factor for OS, particularly in those with limited disease. Further studies are warranted to validate our findings.