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The Stimulator of interferon genes (STING) protein is a critical component of the innate immune response to pathogenic and cytosolic self DNA. The importance of STING signalling has recently been demonstrated in a number of tumor types, including glioblastoma (GBM), and its activation through STING agonism is a promising antitumor therapeutic avenue. Recent studies have shown a loss of STING expression in cancer and an overall dysregulation of the CGAS/STING pathway. A potential mechanism of STING silencing is the methylation of its promoter. Using bulk methylation array data from patient samples, we explore epigenetic control of the TMEM173 gene that encodes STING. We find that the STING promoter is highly methylated in glioblastoma and that STING RNA expression is correspondingly low. Methylation data from normal brain and non-cancer cerebral diseases reveal a consistent pattern of STING promoter hypermethylation in these diverse states. The degree of bulk STING methylation in GBM samples inversely correlates with tumor purity and markers of immune infiltration. Single-cell transcriptome sequencing reveals that STING is expressed specifically in immune cells and endothelial cells, but not glioma cells. Collectively these results suggest that STING signalling is disrupted in GBM, that STING is epigenetically silenced by DNA methylation in the tumor, and that STING expression in bulk GBM tumor samples arises from infiltrating immune cells in the tumor microenvironment. Therapeutic approaches stimulating the innate STING signalling pathway are therefore likely to be effective on infiltrating immune cells rather than tumor cells themselves. This work motivates further study into mechanisms of STING activation in the broader GBM tumor microenvironment.

Objective. To characterize the veterinary pharmacy and pharmacology literature cited by veterinary drug monographs and journal articles and describe the database indexing and availability of this literature in libraries serving pharmacy schools. Methods. Citations in American Academy of Veterinary Pharmacology and Therapeutics monographs, Journal of Veterinary Pharmacology and Therapeutics (JVPT) articles, and Plumb’s Veterinary Drug Handbook, Eighth Edition (Plumb’s) were analyzed for publication type and age. Three zones of cited journals were determined by Bradford’s Law of Scattering based on citation counts. Results. Monographs most often cited journal articles (1886 [64.7%]), unpublished “grey” literature (632 [21.7%]), and books (379 [13.0%]), but only a few cited proceedings (16 [0.5%]). In JVPT, articles predominated (9625 [91.9%]). Articles comprised 54.8% (1,959) of Plumb’s citations; proceedings, 27.0%; books, 15.7%; and grey literature, 2.5%. The age of cited items varied, with 17.1% of monograph citations less than five years old, compared to 26.3% of cited items in JVPT and 40.5% of cited items in Plumb’s being less than five years old. Zone 1 consisted of three veterinary journals for monographs, four veterinary journals for Plumb’s, and 16 veterinary and human journals for JVPT. Indexing coverage was above 92% in Web of Science, Scopus, and PubMed for zone 1 and 2 journals. Libraries serving both pharmacy and veterinary education programs subscribe to 95% of zone 1 journals, while libraries serving pharmacy education at institutions without a veterinary program subscribe to an average of 59% of zone 1 journals. Conclusion. Veterinary pharmacy and pharmacology literature relies on journals from human and veterinary practice, veterinary proceedings, and, less often, books and drug manufacturer information. Libraries supporting pharmacy programs could contribute to the education of future pharmacists who will be filling veterinary prescriptions by increasing access to this literature.