Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China; Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China; Beijing Key Laboratory for Genetics of Birth Defects, MOE Key Laboratory of Major Diseases in Children, Center for Medical Genetics, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
Clin Immunol. 2019 Jun;203:63-71. doi: 10.1016/j.clim.2019.04.006. Epub 2019 Apr 15.
Neuroblastoma is one of the children's malignant tumors with poor prognosis, as well as high recurrence and metastasis rates after surgical removal and chemotherapy. γδ T-cell based immunotherapy receives increasing attention thanks to the strong cytolytic activity to tumor cells. Our previous data revealed a significant increase in circulating γδ T-cell frequency in NB patients. In the present study, we found that beside a reduction of IFN-γ in serum of NB patients, DNAM-1 expression decreased in both circulating and PAM-expanded NB γδ T cells. Upon PAM stimulation, NB γδ T cells showed a reduced level of cell proliferation. In addition, the cytolytic activity of NB γδ T cells to NB cell lines was proved to be attenuated in a co-culture system. The fact that DNAM-1 neutralizing antibody abolished the tumor cell killing accentuates the indispensable role of DNAM-1 molecule in γδ T-cell cytolytic function.
神经母细胞瘤是一种预后不良的儿童恶性肿瘤，手术切除和化疗后复发和转移率较高。基于 γδ T 细胞的免疫疗法因其对肿瘤细胞的强烈细胞溶解活性而受到越来越多的关注。我们之前的数据显示，NB 患者循环 γδ T 细胞频率显著增加。在本研究中，我们发现除了 NB 患者血清中 IFN-γ 减少外，DNAM-1 在循环和 PAM 扩增的 NB γδ T 细胞中的表达也降低。在 PAM 刺激下，NB γδ T 细胞的细胞增殖水平降低。此外，在共培养系统中证实 NB γδ T 细胞对 NB 细胞系的细胞溶解活性减弱。DNAM-1 中和抗体消除肿瘤细胞杀伤的事实强调了 DNAM-1 分子在 γδ T 细胞细胞溶解功能中的不可或缺作用。
