Stimulator of Interferon Genes Protein (STING) Expression in Cancer Cells: A Tissue Microarray Study Evaluating More than 18,000 Tumors from 139 Different Tumor Entities
Author:
Menz Anne1, Zerneke Julia1, Viehweger Florian1, Büyücek Seyma1, Dum David1ORCID, Schlichter Ria1, Hinsch Andrea1, Bawahab Ahmed Abdulwahab2ORCID, Fraune Christoph13, Bernreuther Christian1, Kluth Martina1, Hube-Magg Claudia1ORCID, Möller Katharina1, Lutz Florian1, Reiswich Viktor1, Luebke Andreas M.1ORCID, Lebok Patrick13ORCID, Weidemann Sören A.1, Sauter Guido1, Lennartz Maximilian1ORCID, Jacobsen Frank1, Clauditz Till S.1ORCID, Marx Andreas H.14, Simon Ronald1ORCID, Steurer Stefan1, Burandt Eike1, Gorbokon Natalia1ORCID, Minner Sarah1, Krech Till13
Affiliation:
1. Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 2. Pathology Department, Faculty of Medicine, University of Jeddah, Jeddah 23218, Saudi Arabia 3. Institute of Pathology, Clinical Center Osnabrueck, 49078 Osnabrueck, Germany 4. Department of Pathology, Academic Hospital Fuerth, 90766 Fuerth, Germany
Abstract
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 (p < 0.05). In pTa urothelial carcinomas, STING expression was associated with low-grade carcinoma (p = 0.0002). Across all tumors, STING expression paralleled PD-L1 positivity of tumor and inflammatory cells (p < 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.
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