Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Front Immunol. 2018 Sep 7;9:2021. doi: 10.3389/fimmu.2018.02021. eCollection 2018.
Invariant natural killer T (iNKT) cells produce copious amounts of cytokines in response to T-cell receptor (TCR) stimulation by recognizing antigens such as α-galactosylceramide (α-GalCer) presented on CD1d; thus, orchestrating other immune cells to fight against pathogen infection and tumors. Because of their ability to induce strong anti-tumor responses and the convenience of their invariant TCR activated by a synthetic ligand, α-GalCer, iNKT cells have been intensively studied for application in immunotherapeutic approaches to treat cancer patients in the clinic. Here, we summarize the clinical trials of iNKT cell based immunotherapy for non-small cell lung cancer, and head and neck cancer. Although solid tumors are thought to be refractory to immunotherapeutic approaches, our clinical trials showed that the intravenous injection of α-GalCer-pulsed antigen presenting cells (APCs) activated endogenous iNKT cells and iNKT cell dependent responses. Moreover, an increase in the number of IFN-γ producing cells in PBMCs was associated with prolonged survival. The marked infiltration of iNKT cells and the accumulation of conventional T cells in the tumor microenvironment were also observed after the administration of α-GalCer-pulsed APCs and/or activated iNKT cells. In cases of advanced head and neck squamous cell carcinoma, the increased accumulation of iNKT cells in the tumor microenvironment was correlated with objective clinical responses. We will also discuss potential combination therapies of iNKT cell based immunotherapy to achieve enhanced anti-tumor activity and provide better treatment options for these patients.
天然不变自然杀伤 T(iNKT)细胞在识别 CD1d 上呈现的抗原(如α-半乳糖神经酰胺(α-GalCer))时，通过 T 细胞受体(TCR)刺激产生大量细胞因子；从而协调其他免疫细胞对抗病原体感染和肿瘤。由于其诱导强烈抗肿瘤反应的能力和其不变的 TCR 被合成配体α-GalCer 激活的便利性，iNKT 细胞已被深入研究用于癌症患者的免疫治疗方法。在这里，我们总结了基于 iNKT 细胞的免疫疗法治疗非小细胞肺癌和头颈部癌症的临床试验。尽管实体肿瘤被认为对免疫治疗方法有抗性，但我们的临床试验表明，静脉注射α-GalCer 脉冲抗原呈递细胞(APC)激活内源性 iNKT 细胞和 iNKT 细胞依赖性反应。此外，PBMCs 中 IFN-γ 产生细胞数量的增加与生存时间延长相关。在给予α-GalCer 脉冲 APC 和/或激活的 iNKT 细胞后，也观察到 iNKT 细胞在肿瘤微环境中的明显浸润和常规 T 细胞的积累。在晚期头颈部鳞状细胞癌中，肿瘤微环境中 iNKT 细胞的积累增加与客观临床反应相关。我们还将讨论基于 iNKT 细胞的免疫疗法的潜在联合治疗方法，以实现增强的抗肿瘤活性，并为这些患者提供更好的治疗选择。
