当前位置: X-MOL 学术Med. Microbiol. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
The T cell activating properties and antitumour activity of Staphylococcal Enterotoxin-like Q.
Medical Microbiology and Immunology ( IF 5.4 ) Pub Date : 2019-06-11 , DOI: 10.1007/s00430-019-00614-9
Yanan He 1 , Yuliang Sun 1 , Yakun Ren 2 , Liang Qiao 1, 2 , Rui Guo 2, 3 , Jiang Du 2, 3 , Xinxing Zhu 3 , Yanli Liu 1, 2 , Juntang Lin 1, 2, 3
Affiliation  

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.

中文翻译:

葡萄球菌肠毒素样Q的T细胞活化特性和抗肿瘤活性

葡萄球菌肠毒素(SEs),作为典型的超抗原,在临床上表现出令人鼓舞的抗肿瘤活性,但是它们不可避免的与发烧和呕吐有关的副作用严重限制了它们在恶性肿瘤治疗中的应用。幸运的是,葡萄球菌肠毒素样毒素(SEls)的氨基酸序列与经典SE相似,但不表现出催吐活性或呕吐活性很低,这为癌症治疗提供了一组潜在的免疫调节候选物。这项研究的目的是检查SElQ对淋巴细胞活化的影响,并进一步证明其在体外和体内的抗肿瘤活性。成功收获了高纯度的SElQ,体外结果证实SElQ可以剂量依赖的方式显着激活小鼠和人类来源的淋巴细胞,+和CD8 + T细胞,其百分比和绝对数量均显着增加。进一步检查发现,除了原确认的TCR V β5和21,TCR Vβ14、17和18在SElQ诱导的人PBMC中被激活。此外,在SElQ处理后,IL-2和IFN-γ的表达在体外和体内显着上调。基于SElQ诱导淋巴细胞活化和细胞因子释放的发现,我们然后在体外和体内证实了其抗肿瘤活性。数据显示,低浓度的SElQ(每只小鼠30 µg)治疗可抑制肿瘤生长约30%,并且未观察到明显的毒性。两者合计,我们的结果表明SElQ可以显着诱导T细胞活化和细胞因子释放,并进一步引发实质性的抗肿瘤活性,从而为SElQ在癌症免疫治疗中的潜在应用提供支持。
更新日期:2019-06-11
down
wechat
bug