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The T cell activating properties and antitumour activity of Staphylococcal Enterotoxin-like Q

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Abstract

Staphylococcal enterotoxins (SEs), as typical superantigens, exhibit promising antitumour activity in the clinic, but their unavoidable side effects related to fever and emesis seriously limit their application for the treatment of malignant tumours. Fortunately, the identification of Staphylococcal enterotoxin-like toxins (SEls), which possess amino acid sequences similar to those of classical SEs but exhibit no or low emetic activity, has provided a set of potential immunomodulatory candidates for cancer therapy. The aim of this study was to examine the effect of SElQ on lymphocyte activation and to further demonstrate its antitumour activity both in vitro and in vivo. High-purity SElQ was successfully harvested, and in vitro results confirmed that SElQ can significantly activate mouse- and human-derived lymphocytes in a dose-dependent manner, particularly CD4+ and CD8+ T cells, which showed significant increases in both percentage and absolute number. Further examination revealed that in addition to the originally recognized TCR Vβ5 and 21, TCR Vβ14, 17 and 18 were activated in SElQ-induced human PBMCs. Moreover, the expression of IL-2 and IFN-γ was significantly upregulated in vitro and in vivo after SElQ treatment. Based on the findings that SElQ induces lymphocyte activation and cytokine release, we then confirmed its antitumour activity both in vitro and in vivo. The data showed that treatment with a low concentration of SElQ (30 µg/mouse) could inhibit the growth of tumours by approximately 30% and no significant toxicity was observed. Taken together, our results demonstrated that SElQ can significantly induce T cell activation and cytokine release and further elicit substantial antitumour activity and thus provide support for the potential application of SElQ in cancer immunotherapy.

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Acknowledgements

The authors would like to thank all the teachers and students for their participation in this study.

Funding

This work was financially supported by the National Natural Science Foundation of China (No. 31502045) and Xinxiang Medical University Foundation (No. 2017CXY-2–12 and 20172DCG-03).

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Authors and Affiliations

  1. Stem Cell Research Center, College of Life Science and Technology, Xinxiang Medical University, No. 601 East of JinSui Road, Xinxiang, 453003, Henan, China

    Yanan He, Yuliang Sun, Liang Qiao, Yanli Liu & Juntang Lin

  2. Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang, 453003, China

    Yakun Ren, Liang Qiao, Rui Guo, Jiang Du, Yanli Liu & Juntang Lin

  3. College of Biomedical Engineering, Xinxiang Medical University, Xinxiang, 453003, China

    Rui Guo, Jiang Du, Xinxing Zhu & Juntang Lin

Authors
  1. Yanan He
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  2. Yuliang Sun
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  4. Liang Qiao
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  8. Yanli Liu
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  9. Juntang Lin
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Correspondence to Xinxing Zhu or Yanli Liu.

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The authors declare that they have no conflict of interest.

Ethical approval

The peripheral blood samples used in this study were harvested with the informed consent of the donors, and the experimental procedures performed with the peripheral blood samples were approved by the Ethics Committee of Xinxiang Medical University. Furthermore, the mice handling and experimental procedures were performed with approval from the Animal Care Committee of Xinxiang Medical University in accordance with the guidelines established by the Chinese Council on Animal Care.

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Edited by: Christian Bogdan.

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Yanan He and Yuliang Sun contributed equally to this work.

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He, Y., Sun, Y., Ren, Y. et al. The T cell activating properties and antitumour activity of Staphylococcal Enterotoxin-like Q. Med Microbiol Immunol 208, 781–792 (2019). https://doi.org/10.1007/s00430-019-00614-9

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  • DOI: https://doi.org/10.1007/s00430-019-00614-9

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