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Inhibition of squamous cancer growth in a mouse model by Staphylococcal enterotoxin B-triggered Th9 cell expansion

Cellular & Molecular Immunology volume 14, pages 371–379 (2017)Cite this article

Abstract

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.

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Acknowledgements

This study was supported by grants from the Innovation of Science and Technology Commission of Shenzhen Municipality (JCYJ20140418095735538; JCYJ20120613161724279; JCYJ20120613172559904; JCYJ20130329110735981; JCYJ20120613173233810); International Collaboration Project (GJHZ20130408174112021); and the National Nature Science Foundation and China (81373176).

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Author notes

  1. Bei-Ping Miao and Rui-Shi Zhang: BP Miao and RS Zhang share the first authorship.

  2. Dr PC Yang, Center of Allergy & Immunology, Shenzhen University School of Medicine, 3688 Nanhai Ave., Shenzhen 518060, China. E-mail: pcy2356@szu.edu.cn

  3. ZG Liu, Center of Allergy & Immunology, Shenzhen University School of Medicine, 3688 Nanhai Ave., Shenzhen 518060, China. E-mail: lzg@szu.edu.cn

Authors and Affiliations

  1. Department of Otolaryngology, the First Affiliated Hospital of Shenzhen University and the Second People’s Hospital of Shenzhen, Shenzhen, China

    Bei-Ping Miao, Rui-Shi Zhang, Huan-Ji Sun, Yan-Ping Yu & Tao Chen

  2. Brain Body Institute, McMaster University, Hamilton, L8N 4A6, ON, Canada

    Lin-Jing Li & Jiang-Qi Liu

  3. Shenzhen Women & Children Healthcare, Shenzhen, China

    Jun Liu

  4. Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China

    Bei-Ping Miao, Hai-Qiong Yu, Zhi-Gang Liu & Ping-Chang Yang

  5. Department of Respirology, the First Affiliated Hospital of Shenzhen University and the Second People’s Hospital of Shenzhen, Shenzhen, China

    Min Zhang

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Supplementary information of this article can be found on the Cellular & Molecular Immunology’s website (http://www.nature.com/cmi).

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Miao, BP., Zhang, RS., Sun, HJ. et al. Inhibition of squamous cancer growth in a mouse model by Staphylococcal enterotoxin B-triggered Th9 cell expansion. Cell Mol Immunol 14, 371–379 (2017). https://doi.org/10.1038/cmi.2015.88

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