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cGAS-STING 与癌症:在肿瘤免疫和发展中的双重作用。

cGAS-STING and Cancer: Dichotomous Roles in Tumor Immunity and Development.

机构信息

Department of Integrative Oncology, BC Cancer Agency, Vancouver, Canada; These authors contributed equally to this work.

Centre for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Canada.

出版信息

Trends Immunol. 2018 Jan;39(1):44-54. doi: 10.1016/j.it.2017.07.013. Epub 2017 Aug 19.

Abstract

cGMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) sensing has emerged as a key regulator of innate immune responses to both exogenous and endogenous DNA. Recent studies reveal critical roles for this pathway in natural antitumor immunity across cancer types as well as in immune checkpoint blockade therapy. However, it is also clear that some tumors evade cGAS-STING-mediated immune responses, and immunomodulatory therapeutics are currently being explored to target this pathway. Finally, we also discuss recent observations that cGAS-STING-mediated inflammation may promote tumor initiation, growth, and metastasis in certain malignancies and how this may complicate the utility of this pathway in therapeutic development.

摘要

cGMP-AMP 合成酶 (cGAS)-干扰素基因刺激物 (STING) 感应已成为对外源和内源性 DNA 的先天免疫反应的关键调节剂。最近的研究揭示了该途径在多种癌症类型的天然抗肿瘤免疫以及免疫检查点阻断治疗中的关键作用。然而,也很清楚,一些肿瘤逃避了 cGAS-STING 介导的免疫反应,目前正在探索免疫调节治疗药物来靶向该途径。最后,我们还讨论了最近的观察结果,即 cGAS-STING 介导的炎症可能促进某些恶性肿瘤的肿瘤起始、生长和转移,以及这如何使该途径在治疗开发中的应用复杂化。

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