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

• Published in: Medical microbiology and immunology Vol. 208; no. 6; pp. 781 - 792
• Main Authors: He, Yanan, Sun, Yuliang, Ren, Yakun, Qiao, Liang, Guo, Rui, Du, Jiang, Zhu, Xinxing, Liu, Yanli, Lin, Juntang
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-12-2019; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cancer immunotherapy; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cells, Cultured; Cytokines; Cytokines - metabolism; Dose-Response Relationship, Immunologic; Enterotoxins - metabolism; Female; Fever; Healthy Volunteers; Humans; Immunology; Immunomodulation; Immunotherapy; Interleukin 2; Lymphocyte Activation - drug effects; Lymphocytes; Lymphocytes T; Medical Microbiology; Mice, Inbred BALB C; Original Investigation; Receptors, Antigen, T-Cell - metabolism; Superantigens; Superantigens - metabolism; T cell receptors; Toxicity; Tumors; Virology; Vomiting; γ-Interferon; Superantigen; Staphylococcal enterotoxin; Staphylococcal enterotoxin-like Q; Lymphocyte; Immunotherapy
• ISSN: 0300-8584; 1432-1831
• DOI: 10.1007/s00430-019-00614-9

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
V
β5 and 21, TCR
V
β14, 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.