Recent evidence shows that cyclic GMP-AMP synthase (cGAS)/stimulator of interferon (IFN) genes (STING) signaling is essential for antitumor immunity by inducing the production of type I IFN and thus activating both innate and adaptive immunity based on gene knockout mouse models. However, the extensive detection of the expression of cGAS/STING signaling in human cancer and mining the roles of this signaling pathway in human cancer immunity have not been performed until now. In this study, we revealed that four key molecules (cGAS, STING, TANK binding kinase 1 [TBK1], and IFN regulatory factor 3 [IRF3]) in the cGAS/STING signaling are highly expressed in cancer tissues, and the expression levels of these genes are negatively correlated with their methylation levels in most of the detected cancer types. We also showed that highly upregulated cGAS/STING signaling is negatively correlated with the infiltration of immune cells in some tumor types, and consistent with these findings, we showed that a high level of cGAS/STING signaling predicts a poor prognosis in patients with certain cancers. This study suggests that it is necessary to deeply and fully evaluate the function of cGAS/STING signaling in cancer immunity and cancer progression before the application of the STING agonist-based anticancer immune therapy in the clinic.

最近的证据表明，环状GMP-AMP合酶（cGAS）/干扰素（IFN）基因的刺激物（STING）通过诱导I型IFN的产生从而激活基于基因敲除小鼠的先天免疫和适应性免疫，对于抗肿瘤免疫至关重要楷模。然而，到目前为止，尚未对cGAS / STING信号在人类癌症中的表达进行广泛检测，并探索该信号通路在人类癌症免疫中的作用。在这项研究中，我们揭示了cGAS / STING信号中的四个关键分子（cGAS，STING，TANK结合激酶1 [TBK1]和IFN调节因子3 [IRF3]）在癌症组织中高度表达，并且其表达水平在大多数检测到的癌症类型中，这些基因与其甲基化水平呈负相关。我们还表明，高度上调的cGAS / STING信号传导与某些类型的肿瘤中免疫细胞的浸润负相关，并且与这些发现一致，我们表明，高水平的cGAS / STING信号传导预示着某些癌症患者的预后较差。这项研究表明，在临床上应用基于STING激动剂的抗癌免疫疗法之前，有必要深入全面地评估cGAS / STING信号传导在癌症免疫和癌症进展中的功能。