转移瘤经常从经治疗一级肿瘤后保留的休眠癌细胞中发展而来，这些细胞在免疫规避性的静止状态和易于被免疫介导消除的增殖状态之间波动1-6。目前我们对于如何清除再度唤醒的转移癌细胞及如何通过治疗激活这一过程以消除患者的残存疾病还知之甚少。本文使用至静肺腺癌转移模型识别肿瘤细胞内固有的免疫反应决定因素，以了解其在退出休眠状态时的作用。通过肿瘤内免疫调控器的基因筛选，我们确定STING通路是抑制转移暴发的因素。STING活性在重新进入细胞周期的转移前体细胞中增加，在突破性转移中由STING启动子和增强子的高甲基化或对TGFβ的反应性进入休眠状态时的染色质抑制而减弱。源自自发性转移瘤的癌细胞中STING表达抑制了它们的生长。系统性治疗小鼠STING激动剂可以依赖T细胞和自然杀伤细胞来消除休眠转移和预防自发爆发，这些效应需要癌细胞的STING功能。因此，STING提供了一个针对于休眠转移瘤进展的检查站，并提供了一个治疗上可操作的策略来预防疾病复发。© 2023，本文作者，独家授权给Springer Nature Limited。

Metastasis frequently develops from disseminated cancer cells that remain dormant after the apparently successful treatment of a primary tumour. These cells fluctuate between an immune-evasive quiescent state and a proliferative state liable to immune-mediated elimination1-6. Little is known about the clearing of reawakened metastatic cells and how this process could be therapeutically activated to eliminate residual disease in patients. Here we use models of indolent lung adenocarcinoma metastasis to identify cancer cell-intrinsic determinants of immune reactivity during exit from dormancy. Genetic screens of tumour-intrinsic immune regulators identified the stimulator of interferon genes (STING) pathway as a suppressor of metastatic outbreak. STING activity increases in metastatic progenitors that re-enter the cell cycle and is dampened by hypermethylation of the STING promoter and enhancer in breakthrough metastases or by chromatin repression in cells re-entering dormancy in response to TGFβ. STING expression in cancer cells derived from spontaneous metastases suppresses their outgrowth. Systemic treatment of mice with STING agonists eliminates dormant metastasis and prevents spontaneous outbreaks in a T cell- and natural killer cell-dependent manner-these effects require cancer cell STING function. Thus, STING provides a checkpoint against the progression of dormant metastasis and a therapeutically actionable strategy for the prevention of disease relapse.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.