Stimulator of Interferon Genes Pathway Activation through the Controlled Release of STINGel Mediates Analgesia and Anti-Cancer Effects in Oral Squamous Cell Carcinoma

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dc.citation.articleNumber920en_US
dc.citation.issueNumber4en_US
dc.citation.journalTitleBiomedicinesen_US
dc.citation.volumeNumber12en_US
dc.contributor.authorDong, Minh Phuongen_US
dc.contributor.authorDharmaraj, Neerajaen_US
dc.contributor.authorKaminagakura, Estelaen_US
dc.contributor.authorXue, Jianfeien_US
dc.contributor.authorLeach, David G.en_US
dc.contributor.authorHartgerink, Jeffrey D.en_US
dc.contributor.authorZhang, Michaelen_US
dc.contributor.authorHanks, Hana-Joyen_US
dc.contributor.authorYe, Yien_US
dc.contributor.authorAouizerat, Bradley E.en_US
dc.contributor.authorVining, Kyleen_US
dc.contributor.authorThomas, Carissa M.en_US
dc.contributor.authorDovat, Sinisaen_US
dc.contributor.authorYoung, Simonen_US
dc.contributor.authorViet, Chi T.en_US
dc.date.accessioned2024-07-25T20:55:16Zen_US
dc.date.available2024-07-25T20:55:16Zen_US
dc.date.issued2024en_US
dc.description.abstractOral squamous cell carcinoma (OSCC) presents significant treatment challenges due to its poor survival and intense pain at the primary cancer site. Cancer pain is debilitating, contributes to diminished quality of life, and causes opioid tolerance. The stimulator of interferon genes (STING) agonism has been investigated as an anti-cancer strategy. We have developed STINGel, an extended-release formulation that prolongs the availability of STING agonists, which has demonstrated an enhanced anti-tumor effect in OSCC compared to STING agonist injection. This study investigates the impact of intra-tumoral STINGel on OSCC-induced pain using two separate OSCC models and nociceptive behavioral assays. Intra-tumoral STINGel significantly reduced mechanical allodynia in the orofacial cancer model and alleviated thermal and mechanical hyperalgesia in the hind paw model. To determine the cellular signaling cascade contributing to the antinociceptive effect, we performed an in-depth analysis of immune cell populations via single-cell RNA-seq. We demonstrated an increase in M1-like macrophages and N1-like neutrophils after STINGel treatment. The identified regulatory pathways controlled immune response activation, myeloid cell differentiation, and cytoplasmic translation. Functional pathway analysis demonstrated the suppression of translation at neuron synapses and the negative regulation of neuron projection development in M2-like macrophages after STINGel treatment. Importantly, STINGel treatment upregulated TGF-β pathway signaling between various cell populations and peripheral nervous system (PNS) macrophages and enhanced TGF-β signaling within the PNS itself. Overall, this study sheds light on the mechanisms underlying STINGel-mediated antinociception and anti-tumorigenic impact.en_US
dc.identifier.citationDong, M. P., Dharmaraj, N., Kaminagakura, E., Xue, J., Leach, D. G., Hartgerink, J. D., Zhang, M., Hanks, H.-J., Ye, Y., Aouizerat, B. E., Vining, K., Thomas, C. M., Dovat, S., Young, S., & Viet, C. T. (2024). Stimulator of Interferon Genes Pathway Activation through the Controlled Release of STINGel Mediates Analgesia and Anti-Cancer Effects in Oral Squamous Cell Carcinoma. Biomedicines, 12(4), Article 4. https://doi.org/10.3390/biomedicines12040920en_US
dc.identifier.digitalbiomedicines-12-00920en_US
dc.identifier.doihttps://doi.org/10.3390/biomedicines12040920en_US
dc.identifier.urihttps://hdl.handle.net/1911/117508en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleStimulator of Interferon Genes Pathway Activation through the Controlled Release of STINGel Mediates Analgesia and Anti-Cancer Effects in Oral Squamous Cell Carcinomaen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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