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一种可提高NK细胞抗肿瘤疗效的新靶标
来源: | 作者:prod821c5 | 发布时间: 2017-12-04 | 1025 次浏览 | 分享到:

默赛尔生物原创,欢迎转载,敬请注明来源

       在肿瘤的常规治疗如化疗、放疗、热疗和细胞因子治疗过程中,免疫细胞被认为参与启动抗肿瘤效应。可用于解释这一过程的机制之一是所谓的压力诱导的免疫刺激配体的表达。活化性受体NKG2D已被证明可通过靶向它的配体发挥抗肿瘤效应,但另一种重要的活化性受体NKp30却很少被提及。该研究发现NKp30的配体B7-H6广泛表达于多数肿瘤细胞表面,与它们对NK细胞裂解作用的敏感性密切相关。进一步研究显示几乎所有的肿瘤常规治疗手段都可以上调肿瘤细胞表面B7-H6的表达,同时增强肿瘤细胞对NK裂解的敏感性。B7-H6 shRNA处理可有效降低肿瘤细胞对NK介导的裂解作用的敏感性。该研究不仅表明肿瘤疗法可作为应力诱导因子促进肿瘤对NK细胞裂解的敏感性,而且未来可将B7-H6作为潜在的靶标应用于肿瘤的临床治疗中。

原文摘要

Immune cells are believed to participate in initiating anti-tumor effects during regular tumor therapy such as chemotherapy, radiation, hyperthermia and cytokine injection.One of the mechanisms underlying this process is the expression of so-called stress-inducible immunostimulating ligands. Although the activating receptor NKG2D has been proven to play roles in tumor therapy through targeting its ligands, the role of NKp30, another key activating receptor, is seldom addressed. In this study, we found that the NKp30 ligand B7-H6 was widely expressed in tumor cells and closely correlated to their susceptibility to NK cell lysis. Further studies showed that treatment of tumor cells with almost all standard tumor therapeutics, including chemotherapy (cisplatin,5-fluorouracil), radiation therapy, non-lethal heat shock, and cytokine therapy(TNF-α), could upregulate the expression of B7-H6 in tumor cells and enhance tumor sensitivity to NK cell cytolysis. B7-H6 shRNA treatment effectively dampened sensitization of tumor cells to NK-mediated lysis. Our study not only reveals the possibility that tumor therapeutics work as stress inducers to enhance tumor sensitivity to NK cell cytolysis but also suggests that B7-H6 could be a potential target for tumor therapy in the future.

Cao G., et al.(2015). Tumor therapeutics work as stress inducers to enhance tumor sensitivity to NK cell cytolysis by upregulating NKp30 ligand B7-H6. J Biol Chem. 2015 Oct 15. pii: jbc.M115.674010.