Okamoto Yoshitaka, Fujikawa Akira, Kurosaki Motoyoshi, Yamasaki Kazuki, Sakurai Daijyu, Horiguchi Shigetoshi, Nakayama Toshinori
Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University Hospital, and Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Adv Otorhinolaryngol. 2011;72:149-52. doi: 10.1159/000324775. Epub 2011 Aug 18.
Human NKT cells are known to have strong antitumor activities and to be activated by specific ligand, α-galactosylceramide (αGelCer). We examined the migration pattern of αGalCer-pulsed DCs and the immune responses after administration by different routes. DCs injected into nasal submucosa quickly migrated to the lateral neck lymph rather than the lateral lymph nodes. The absolute number of NKT cells and the IFN-γ-producing cells increased in peripheral blood after injection of the DCs into nasal submucosa. We conducted a phase I study with αGalCer-pulsed DCs administered in nasal submucosa of patients with head and neck cancer, and evaluated safety and feasibility. The results showed that nasal submucosal administration of α-GalCer-pulsed DCs was safe and a smaller number of these DCs could exhibit significant immune responses and some positive clinical effects. In additional study, the use of the intra-arterial infusion of activated NKT cells and the submucosal injection of α-GalCer-pulsed DCs has been shown to induce significant antitumor immunity and had beneficial clinical effects in the management of advanced head and neck squamous cell carcinoma. The NKT cell-based cancer immunotherapy may be helpful in management of head and neck cancer and needs to be explored in further detail.
已知人类自然杀伤T细胞（NKT细胞）具有强大的抗肿瘤活性，并可被特定配体α-半乳糖神经酰胺（αGelCer）激活。我们研究了用αGelCer脉冲处理的树突状细胞（DCs）的迁移模式以及不同给药途径后的免疫反应。注入鼻黏膜下层的DCs迅速迁移至颈部外侧淋巴结而非外侧淋巴结。将DCs注入鼻黏膜下层后，外周血中NKT细胞和产生γ干扰素的细胞的绝对数量增加。我们对αGelCer脉冲处理的DCs经鼻黏膜下层给药用于头颈癌患者进行了I期研究，并评估了安全性和可行性。结果表明，经鼻黏膜下层给予α-GelCer脉冲处理的DCs是安全的，且较少量的这些DCs就能产生显著的免疫反应和一些积极的临床效果。在进一步的研究中，动脉内输注活化的NKT细胞和经黏膜下层注射αGelCer脉冲处理的DCs已被证明可诱导显著的抗肿瘤免疫，并对头颈部晚期鳞状细胞癌的治疗产生有益的临床效果。基于NKT细胞的癌症免疫疗法可能对头颈部癌症的治疗有帮助，需要进一步详细探索。
