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

Our plain-English summary of 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, by A. Menz, J. Zerneke, F. Viehweger, et al (Cancers, 2024).

The study

• Authors: A. Menz, J. Zerneke, F. Viehweger, S. Büyücek, D. Dum, R. Schlichter, A. Hinsch, A.A. Bawahab, C. Fraune, C. Bernreuther, M. Kluth, C. Hube-Magg, K. Möller, F. Lutz, V. Reiswich, A.M. Luebke, P. Lebok, S.A. Weidemann, G. Sauter, M. Lennartz, F. Jacobsen, T.S. Clauditz, A.H. Marx, R. Simon, S. Steurer, E. Burandt, N. Gorbokon, S. Minner, T. Krech
• Journal: Cancers
• Published: 2024;16(13)
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory study used tissue microarrays (small tissue spots on slides) to look for a protein called STING in 18,001 tumor samples from 139 tumor types, plus 608 normal tissue samples. The samples came from pathology archives in Hamburg, Osnabrueck and Fuerth, Germany. STING was stained with an antibody, and 15,345 tumor samples could be evaluated. Tumor-cell STING staining was found in 8908 (58.1%) of them. Among malignant mesotheliomas, 88.5% of 26 evaluable epithelioid tumors and 95.7% of 46 evaluable biphasic tumors were STING-positive. The article did not say whether these mesotheliomas were pleural or peritoneal, and it did not study asbestos exposure. High STING expression was statistically linked to adverse features in breast, clear cell kidney, colorectal, liver and papillary thyroid cancers. In non-invasive bladder cancer it was linked instead to low grade. Across all tumors, STING went along with PD-L1 positivity (p less than 0.0001) but not with the density of CD8-positive immune cells (p = 0.4253). The authors concluded that high STING expression, rather than its absence, tends to be linked to a more aggressive cancer phenotype.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cross-sectional laboratory study (immunohistochemistry on pre-existing tissue microarrays), with a survival analysis in a breast cancer subgroup
• Who was studied: 18,001 primary tumor samples from 139 tumor types and subtypes, plus a normal-tissue array of 608 samples from 76 normal tissue types. The samples came from archives in Hamburg, Osnabrueck and Fuerth, Germany. They included 40 epithelioid and 77 biphasic mesotheliomas, of which 26 and 46 were analyzable. Dates of collection were not given.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The study measured STING protein in tumor cells by immunohistochemistry with the mouse monoclonal antibody MSVA-515M, checked in normal tissues against a second antibody, D2P2F.
• Main results:
  • 15,345 (85.2%) of the 18,001 tumor samples were interpretable.
  • Tumor-cell STING positivity was found in 8908 (58.1%) of the 15,345 analyzable tumors.
  • Malignant mesothelioma showed STING positivity in 88.5% to 95.7% of cases. Epithelioid mesothelioma (26 analyzable): 11.5% negative and 15.4% strong. Biphasic mesothelioma (46 analyzable): 4.3% negative and 45.7% strong.
  • In clear cell renal cell carcinoma, high STING expression was linked to poor histologic grade (p less than 0.005), high pT category (p less than 0.0001) and high UICC stage (p = 0.0060).
  • In colorectal adenocarcinoma, high STING expression was linked to right-side tumor location (p = 0.0008), microsatellite instability (p = 0.0016) and RAS mutations (p less than 0.0001).
  • High STING expression was related to nodal metastases in hepatocellular carcinoma (p = 0.0435) and in papillary thyroid carcinoma (p = 0.0074).
  • In invasive breast cancer of no special type, high STING expression was linked to poor overall survival (p = 0.0196).
  • In non-invasive urothelial carcinoma of the bladder, high STING expression was associated with low grade (p = 0.0002).
  • Across all tumor entities, high STING expression in tumor cells was associated with PD-L1 positivity of tumor cells and of tumor-associated inflammatory cells (p less than 0.0001 each).
  • STING expression was unrelated to the density of CD8-positive cells (p = 0.4253; data from 5880 tumors).
• The authors' conclusion: The authors concluded that high STING expression, rather than STING deficiency, tends to be linked to a more aggressive cancer phenotype. They also concluded that STING in tumor cells is tightly linked to PD-L1 expression but may not measurably affect the number of tumor-infiltrating inflammatory cells.

Topics

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Squamous Cell Carcinoma, Mesothelioma, Adenocarcinoma, Ovarian Cancer, Carcinoma, PD-L1.

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