Menz Anne, Zerneke Julia, Viehweger Florian, Büyücek Seyma, Dum David, Schlichter Ria, Hinsch Andrea, Bawahab Ahmed Abdulwahab, Fraune Christoph, Bernreuther Christian, Kluth Martina, Hube-Magg Claudia, Möller Katharina, Lutz Florian, Reiswich Viktor, Luebke Andreas M, Lebok Patrick, Weidemann Sören A, Sauter Guido, Lennartz Maximilian, Jacobsen Frank, Clauditz Till S, Marx Andreas H, Simon Ronald, Steurer Stefan, Burandt Eike, Gorbokon Natalia, Minner Sarah, Krech Till
Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Pathology Department, Faculty of Medicine, University of Jeddah, Jeddah 23218, Saudi Arabia.
Cancers (Basel). 2024 Jun 30;16(13):2425. doi: 10.3390/cancers16132425.
Stimulator of interferon genes protein (STING) activates the immune response in inflammatory cells. STING expression in cancer cells is less well characterized, but STING agonists are currently being evaluated as anticancer drugs. A tissue microarray containing 18,001 samples from 139 different tumor types was analyzed for STING by immunohistochemistry. STING-positive tumor cells were found in 130 (93.5%) of 139 tumor entities. The highest STING positivity rates occurred in squamous cell carcinomas (up to 96%); malignant mesothelioma (88.5%-95.7%); adenocarcinoma of the pancreas (94.9%), lung (90.3%), cervix (90.0%), colorectum (75.2%), and gallbladder (68.8%); and serous high-grade ovarian cancer (86.0%). High STING expression was linked to adverse phenotypes in breast cancer, clear cell renal cell carcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, and papillary carcinoma of the thyroid ( < 0.05). In pTa urothelial carcinomas, STING expression was associated with low-grade carcinoma ( = 0.0002). Across all tumors, STING expression paralleled PD-L1 positivity of tumor and inflammatory cells ( < 0.0001 each) but was unrelated to the density of CD8+ lymphocytes. STING expression is variable across tumor types and may be related to aggressive tumor phenotype and PD-L1 positivity. The lack of relationship with tumor-infiltrating CD8+ lymphocytes argues against a significant IFN production by STING positive tumor cells.
干扰素基因刺激蛋白（STING）可激活炎症细胞中的免疫反应。癌细胞中STING的表达特征尚不明确，但目前正在评估STING激动剂作为抗癌药物的效果。通过免疫组织化学分析了一个包含来自139种不同肿瘤类型的18001个样本的组织微阵列中的STING。在139个肿瘤实体中的130个（93.5%）中发现了STING阳性肿瘤细胞。STING阳性率最高的是鳞状细胞癌（高达96%）；恶性间皮瘤（88.5%-95.7%）；胰腺腺癌（94.9%）、肺癌（90.3%）、子宫颈癌（90.0%）、结直肠癌（75.2%）和胆囊癌（68.8%）；以及浆液性高级别卵巢癌（86.0%）。STING高表达与乳腺癌、透明细胞肾细胞癌、结直肠腺癌、肝细胞癌和甲状腺乳头状癌的不良表型相关（P<0.05）。在pTa尿路上皮癌中，STING表达与低级别癌相关（P=0.0002）。在所有肿瘤中，STING表达与肿瘤及炎症细胞的PD-L1阳性平行（均P<0.0001），但与CD8+淋巴细胞密度无关。STING表达在不同肿瘤类型中存在差异，可能与侵袭性肿瘤表型和PD-L1阳性有关。与肿瘤浸润性CD8+淋巴细胞缺乏相关性表明STING阳性肿瘤细胞不会大量产生干扰素。
