Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma
Low levels of circulating invariant natural killer T cells predict poor clinical outcome in patients with head and neck squamous cell carcinoma
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DOI：
10.1200/jco.2006.08.5787
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发表时间：
2007-03-01
影响因子：
45.3
通讯作者：
van den Eertwegh, Alfons J. M.
中科院分区：
文献类型：
--
作者：
Molling, Johan W.;Langius, Jacqueline A. E.;van den Eertwegh, Alfons J. M.
目的逃避抗肿瘤免疫反应是头颈部鳞状细胞癌（HNSCC）发病机制的一个重要方面。不变性cd1限制性自然杀伤T细胞（iNKT）据称通过免疫效应细胞的反激活在这些反应中起关键作用。据报道，与健康对照相比，癌症患者外周血中的iNKT细胞减少。在这里，我们研究了这种缺陷的程度是否会影响HNSCC患者的疾病结局。在一项前瞻性研究中，对47例放疗前患者的循环iNKT细胞数量进行了评估。根据iNKT细胞水平将患者分为三组，在中位31个月的随访期间获得临床数据。结果：与中等或较大的循环iNKT细胞分数相比，较小的循环iNKT细胞分数与HNSCC患者3年总生存率（分别为39% v 75%和92%）、疾病特异性生存率（分别为43% v 87%和92%）和局部区域控制率（分别为31% v74%和92%）的降低显著相关。Cox回归显示，即使校正了年龄的混杂效应，iNKT细胞水平和临床T分期仍是一个独立的预后参数。结论严重的循环iNKT细胞缺乏与HNSCC患者临床预后差有关，提示其在抗肿瘤免疫应答中起重要作用。此外，iNKT细胞水平的筛查可能有助于确定哪些患者可以从旨在重建循环iNKT细胞池的免疫辅助治疗中获益。
Purpose Evading antitumor immune responses is an important aspect of the pathogenesis of head and neck squamous cell carcinoma (HNSCC). Invariant CD1d-restricted natural killer T (iNKT) cells play an allegedly pivotal role in such responses via transactivation of immune effector cells. It has been reported that iNKT cells are reduced in peripheral blood of cancer patients compared with healthy controls. Here, we investigated whether the extent of this deficiency affected disease outcome in HNSCC patients.Patients and Methods In a prospective study, circulating iNKT cell numbers were evaluated in 47 patients before radiotherapy. Patients were stratified in three groups based on iNKT cell levels, and clinical data were obtained during a median follow-up period of 31 months.Results A small, compared with an intermediate or large, circulating iNKT cell fraction was significantly associated with decreased 3-year overall survival rate (39% v 75% and 92%, respectively), disease-specific survival rate (43% v 87% and 92%, respectively), and locoregional control rate (31% v74% and 92%, respectively) in HNSCC patients. Cox regression revealed that the iNKT cell level, as well as clinical T stage, was an independent prognostic parameter even after correction for the confounding effect of age.Conclusion A severe circulating iNKT cell deficiency was related to poor clinical outcome in HNSCC patients, suggesting their critical contribution to antitumor immune responses. Furthermore, screening for iNKT cell levels may be useful for determining which patients can benefit from immunotherapeutic adjuvant therapies aimed at reconstitution of the circulating iNKT cell pool.