STING signaling in cancer is a crucial component of response to immunotherapy and other anti-cancer treatments. Currently, there is no robust method of measuring STING activation in cancer. Here, we describe an immunohistochemistry-based assay with digital pathology assessment of STING in tumor cells. Using this novel approach in estrogen receptor-positive (ER+) and ER- breast cancer, we identify perinuclear-localized expression of STING (pnSTING) in ER+ cases as an independent predictor of good prognosis, associated with immune cell infiltration and upregulation of immune checkpoints. Tumors with low pnSTING are immunosuppressed with increased infiltration of “M2”-polarized macrophages. In ER- disease, pnSTING does not appear to have a significant prognostic role with STING uncoupled from interferon responses. Importantly, a gene signature defining low pnSTING expression is predictive of poor prognosis in independent ER+ datasets. Low pnSTING is associated with chromosomal instability, MYC amplification and mTOR signaling, suggesting novel therapeutic approaches for this subgroup.

癌症中的 STING 信号传导是免疫疗法和其他抗癌治疗反应的重要组成部分。目前，还没有可靠的方法来测量癌症中 STING 的激活。在这里，我们描述了一种基于免疫组织化学的检测方法，对肿瘤细胞中的 STING 进行数字病理学评估。在雌激素受体阳性 (ER+) 和 ER- 乳腺癌中使用这种新方法，我们确定 ER+ 病例中核周局部表达 STING (pnSTING) 作为良好预后的独立预测因子，与免疫细胞浸润和免疫检查点上调相关。pnSTING 低的肿瘤因“M2”极化巨噬细胞浸润增加而受到免疫抑制。在 ER 疾病中，pnSTING 似乎没有显着的预后作用，因为 STING 与干扰素反应无关。重要的是，定义低 pnSTING 表达的基因特征可以预测独立 ER+ 数据集中的不良预后。低 pnSTING 与染色体不稳定、 MYC扩增和 mTOR 信号传导相关，这表明该亚组有新的治疗方法。