肺腺癌PET/CT代谢指标与免疫细胞标志物表达水平的相关性

Correlation of PET/CT metabolic makers with expression of immune cell markers in patients with lung adenocarcinoma

目的:分析肺腺癌18F-FDG PET/CT代谢指标与免疫细胞标志物表达水平的相关性,探讨其在肺腺癌治疗及判断预后中的作用。方法:回顾性分析2008年4月至2014年8月在天津医科大学肿瘤医院收治并接受PET/CT检查的85例肺腺癌患者的临床资料,应用免疫组织化学法检测癌组织中CD3、CD8、CD68、CD163、CD11c、Foxp3、PD-1和PD-L1的表达水平,采用Pearson相关性检验PET/CT各指标[肿瘤原发灶最大摄取标准值(SUVmax)、标准摄取值峰值(SUVpeak)和平均标准摄取值(SUVmean)]与CD68+肿瘤相关巨噬细胞(CD68+TAM)和肿瘤代谢指标[肿瘤代谢体积(MTV)、糖酵解总量(TLG)]的相关性,Kaplan-Meier法分析肿瘤代谢与免疫指标和患者生存的相关性。结果:SUVmax、SUVpeak和SUVmean与CD68+TAM的表达水平在肺腺癌患者中呈负相关(r=-0.253、-0.265、-0.263,均P<0.05),与PD-1+TIL表达水平呈正相关(r=0.427、0.402、0.395,均P<0.01)。MTV、TLG与Foxp3+Treg、PD-1+TIL表达水平呈正相关(r=0.313、0.307、0.29、0.407,均P<0.01)。Kaplan-Meier法生存分析发现,SUVmax、SUVmean、CD11c+DC、PD-L1+细胞和TLG水平与患者预后(PFS或OS)显著相关(均P<0.05)。结论:肿瘤原发灶代谢状态与肿瘤浸润免疫细胞标志物表达显著相关,该两项中的部分指标与患者预后显著相关,提示18F-FDG PET/CT检测指标反映的肿瘤代谢和微环境免疫状态对肺腺癌患者预后判断及免疫治疗具有重要的参考价值。

Objective:To investigate the relationship between 18F-FDG PET/CT metabolic indicators and expression of immunocyte markers in lung adenocarcinoma patients,and to explore its significance in treatment and prognosis prediction for lung adenocarcinoma patients.Methods:The clinical data of 85 lung adenocarcinoma patients,who admitted to Tianjin Medical University Cancer Institute and Hospital and underwent PET/CT examination from April 2008 to August 2014,were retrospectively analyzed.The expression levels of CD3,CD8,CD68,CD163,CD11c,Foxp3,PD-1 and PD-L1 were determined by immunohistochemistry.Correlations among immune markers(CD68+TAM),PET/CT metabolic parameters(SUVmax,SUVpeak and SUVmean)and tumor metabolic indicators(MTV,TLG)were analyzed using Pearson correlation analysis.The relationships between tumor metabolism,immune indicators and patients’survival outcomes were analyzed using the Kaplan-Meier method.Results:There was a remarkably negative correlation between SUVmax,SUVpeak,SUVmean and expression level of CD68+TAMs(r=-0.253,-0.265,-0.263,all P<0.05)but positive correlation with PD-1+TILs(r=0.427,0.402,0.395,all P<0.01)in lung adenocarcinoma patients.MTV and TLG were positively associated with Foxp3+ Tregs and PD-1+ TILs(r=0.313,0.307,0.29,0.407,all P<0.01).Kaplan-Meier survival analysis showed that SUVmax,SUVmean,CD11c+DCs,PD-L1+ cells and TLG were all significantly associated with patients’prognosis(PFS or OS)(all P<0.05).Conclusion:Metabolism of tumor primary lesions is significantly correlated with tumor infiltrating immunocytes,and some of these indicators were associated with patients’prognosis,suggesting that tumor metabolism and microenvironment immune status reflected by 18F-FDG PET/CT indicators may have important reference value for the immunotherapy and prognosis prediction of lung adenocarcinoma patients.