Miao Bei-Ping, Zhang Rui-Shi, Sun Huan-Ji, Yu Yan-Ping, Chen Tao, Li Lin-Jing, Liu Jiang-Qi, Liu Jun, Yu Hai-Qiong, Zhang Min, Liu Zhi-Gang, Yang Ping-Chang
Department of Otolaryngology, the First Affiliated Hospital of Shenzhen University and the Second People's Hospital of Shenzhen, Shenzhen, China.
Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Cell Mol Immunol. 2017 Apr;14(4):371-379. doi: 10.1038/cmi.2015.88. Epub 2015 Sep 21.
Currently, therapy for squamous cancer (SqC) is unsatisfactory. Staphylococcal enterotoxin B (SEB) has strong immune regulatory activity. This study tests the hypothesis that SEB enforces the effect of immunotherapy on SqC growth in a mouse model. C3H/HeN mice and the SqC cell line squamous cell carcinoma VII were used to create an SqC mouse model. Immune cell assessment was performed by flow cytometry. Real-time RT-PCR and western blotting were used to evaluate target molecule expression. An apoptosis assay was used to assess the suppressive effect of T helper-9 (Th9) cells on the SqC cells. The results showed that immunotherapy consisting of SEB plus SqC antigen significantly inhibited SqC growth in the mice. The frequency of Th9 cells was markedly increased in the SqC tissue and mouse spleens after treatment. SEB markedly increased the levels of signal transducer and activator of transcription 5 phosphorylation and the expression of histone deacetylase-1 (HDAC1) and PU.1 (the transcription factor of the interleukin 9 (IL-9) gene) in CD4 T cells. Exposure to SqC-specific Th9 cells markedly induced SqC cell apoptosis both in vitro and in vivo. In conclusion, the administration of SEB induces Th9 cells in SqC-bearing mice, and theseTh9 cells inhibit SqC growth.
目前，鳞状细胞癌（SqC）的治疗效果并不理想。葡萄球菌肠毒素B（SEB）具有强大的免疫调节活性。本研究检验了以下假设：在小鼠模型中，SEB可增强免疫疗法对SqC生长的作用。采用C3H/HeN小鼠和SqC细胞系鳞状细胞癌VII构建SqC小鼠模型。通过流式细胞术进行免疫细胞评估。采用实时逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法评估靶分子表达。通过凋亡检测评估辅助性T细胞9（Th9）对SqC细胞的抑制作用。结果显示，由SEB加SqC抗原组成的免疫疗法显著抑制了小鼠体内SqC的生长。治疗后，SqC组织和小鼠脾脏中Th9细胞的频率显著增加。SEB显著提高了CD4 T细胞中信号转导子和转录激活子5的磷酸化水平以及组蛋白去乙酰化酶-1（HDAC1）和PU.1（白细胞介素9（IL-9）基因的转录因子）的表达。暴露于SqC特异性Th9细胞在体外和体内均显著诱导SqC细胞凋亡。总之，给予SEB可在荷SqC小鼠体内诱导Th9细胞，且这些Th9细胞可抑制SqC生长。
