Hishiki Tomoro, Mise Naoko, Harada Kazuaki, Ihara Fumie, Takami Mariko, Saito Takeshi, Terui Keita, Nakata Mitsuyuki, Komatsu Shugo, Yoshida Hideo, Motohashi Shinichiro
Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Division of Surgical Oncology, Children's Cancer Center, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
Pediatr Surg Int. 2018 Feb;34(2):195-201. doi: 10.1007/s00383-017-4189-x. Epub 2017 Oct 10.
Tumor immunity has been suggested to play a key role in clinical and biological behavior of neuroblastomas. Given that CD1-restricted invariant natural killer T (iNKT) cells enhance both innate and acquired tumor immunity, we investigated the expression of the iNKT-cell-specific T-cell receptor Vα24-Jα18 in neuroblastoma tissues and its correlation with clinical and biological characteristics.
Using real- time quantitative PCR, we quantified the expression of Vα24-Jα18 in untreated tumor samples from 107 neuroblastoma cases followed in our institution and analyzed the correlation between the presence of infiltrated iNKT cells and clinical characteristics or patients' outcome.
Vα24-Jα18 receptor was detected in 62 untreated cases (57.9%). The expression was significantly higher in stages 1, 2, 3, or 4S (P = 0.0099), in tumors with low or intermediate risk (P = 0.0050), with high TrkA expression (P = 0.0229), with favorable histology (P = 0.0026), with aneuploidy (P = 0.0348), and in younger patients (P = 0.0036). The overall survival rate was significantly higher in patients with iNKT-cell infiltration (log-rank; P = 0.0089).
Since tumor-infiltrating iNKT cells were predominantly observed in neuroblastomas undergoing spontaneous differentiation and/or regression, we suggest that iNKT cells might play a key role in these processes.
肿瘤免疫被认为在神经母细胞瘤的临床和生物学行为中起关键作用。鉴于CD1限制性不变自然杀伤T(iNKT)细胞可增强先天性和获得性肿瘤免疫,我们研究了iNKT细胞特异性T细胞受体Vα24-Jα18在神经母细胞瘤组织中的表达及其与临床和生物学特征的相关性。
我们使用实时定量PCR对本机构随访的107例神经母细胞瘤患者未经治疗的肿瘤样本中Vα24-Jα18的表达进行定量,并分析浸润的iNKT细胞的存在与临床特征或患者预后之间的相关性。
在62例未经治疗的病例(57.9%)中检测到Vα24-Jα18受体。在1、2、3或4S期(P = 0.0099)、低或中危肿瘤(P = 0.0050)、TrkA高表达(P = 0.0229)、组织学良好(P = 0.0026)、非整倍体(P = 0.0348)以及年轻患者(P = 0.0036)中,该表达显著更高。iNKT细胞浸润患者的总生存率显著更高(对数秩检验;P = 0.0089)。
由于在经历自发分化和/或消退的神经母细胞瘤中主要观察到肿瘤浸润性iNKT细胞,我们认为iNKT细胞可能在这些过程中起关键作用。