JCO：炎症细胞在转移性神经母细胞瘤中的临床意义

年龄在18个月或以上的患有转移性神经母细胞瘤的儿童诊断时通常发现，肿瘤相关炎症基因表达的提高似乎与预后不良相关，据8月27日在线发表在Journal of Clinical Oncology杂志上的一则研究证实。

洛杉矶儿童医院Shahab Asgharzadeh, MD和他的同事研究与肿瘤相关炎症细胞相关的基因是否与生存期有关。免疫组化对71例局部和转移性神经母细胞瘤的肿瘤相关巨噬细胞（TAMs）进行了研究。无进展生存期的预测是基于对133例转移性NBL-NAS患者体内44个肿瘤和炎症基因进行评估后得出来的。

该研究结果在参加两个额外研究中的9 1例高风险的肿瘤患者身上得到了验证。研究人员观察到TAMs浸润的增加局部肿瘤恶化成转移性神经母细胞瘤。与患者在诊断时更年轻时相比，患者在诊断时年龄在18个月或以上时，炎症相关基因的表达是增高的。一种新型的准确性的14个肿瘤分类基因得分高出百分之二十五是由于TAMs表达了其中5个基因。研究报告首次证实了瘤内炎症在转移性神经母细胞瘤中的作用，并为转移性NBL-NA儿童提供了一个有效的预后指标。这项研究部分由安进公司资助。

doi:10.1200/JCO.2011.40.9169
PMC:
PMID:

Clinical Significance of Tumor-Associated Inflammatory Cells in Metastatic Neuroblastoma

Shahab Asgharzadeh, Jill A. Salo, Lingyun Ji, André Oberthuer, Matthias Fischer, et al.

Purpose Children diagnosed at age ≥ 18 months with metastatic MYCN-nonamplified neuroblastoma (NBL-NA) are at high risk for disease relapse, whereas those diagnosed at age < 18 months are nearly always cured. In this study, we investigated the hypothesis that expression of genes related to tumor-associated inflammatory cells correlates with the observed differences in survival by age at diagnosis and contributes to a prognostic signature.

Methods Tumor-associated macrophages (TAMs) in localized and metastatic neuroblastomas (n = 71) were assessed by immunohistochemistry. Expression of 44 genes representing tumor and inflammatory cells was quantified in 133 metastatic NBL-NAs to assess age-dependent expression and to develop a logistic regression model to provide low- and high-risk scores for predicting progression-free survival (PFS). Tumors from high-risk patients enrolled onto two additional studies (n = 91) served as independent validation cohorts.

Results Metastatic neuroblastomas had higher infiltration of TAMs than locoregional tumors, and metastatic tumors diagnosed in patients at age ≥ 18 months had higher expression of inflammation-related genes than those in patients diagnosed at age < 18 months. Expression of genes representing TAMs (CD33/CD16/IL6R/IL10/FCGR3) contributed to 25% of the accuracy of a novel 14-gene tumor classification score. PFS at 5 years for children diagnosed at age ≥ 18 months with NBL-NA with a low- versus high-risk score was 47% versus 12%, 57% versus 8%, and 50% versus 20% in three independent clinical trials, respectively.

Conclusion These data suggest that interactions between tumor and inflammatory cells may contribute to the clinical metastatic neuroblastoma phenotype, improve prognostication, and reveal novel therapeutic targets.