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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Autor(es): dc.contributorLoma Linda University-
Autor(es): dc.contributorThe University of Texas Health Science Center at Houston-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorRice University-
Autor(es): dc.contributorNew York University College of Dentistry-
Autor(es): dc.contributorUniversity of Pennsylvania-
Autor(es): dc.contributorUniversity of Alabama at Birmingham-
Autor(es): dc.contributorPennsylvania State University College of Medicine-
Autor(es): dc.creatorDong, Minh Phuong-
Autor(es): dc.creatorDharmaraj, Neeraja-
Autor(es): dc.creatorKaminagakura, Estela-
Autor(es): dc.creatorXue, Jianfei-
Autor(es): dc.creatorLeach, David G.-
Autor(es): dc.creatorHartgerink, Jeffrey D.-
Autor(es): dc.creatorZhang, Michael-
Autor(es): dc.creatorHanks, Hana-Joy-
Autor(es): dc.creatorYe, Yi-
Autor(es): dc.creatorAouizerat, Bradley E.-
Autor(es): dc.creatorVining, Kyle-
Autor(es): dc.creatorThomas, Carissa M.-
Autor(es): dc.creatorDovat, Sinisa-
Autor(es): dc.creatorYoung, Simon-
Autor(es): dc.creatorViet, Chi T.-
Data de aceite: dc.date.accessioned2025-08-21T17:39:42Z-
Data de disponibilização: dc.date.available2025-08-21T17:39:42Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2024-04-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.3390/biomedicines12040920-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/308283-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/308283-
Descrição: dc.descriptionOral 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.-
Descrição: dc.descriptionFour Diamonds-
Descrição: dc.descriptionDepartment of Oral and Maxillofacial Surgery School of Dentistry Loma Linda University-
Descrição: dc.descriptionKatz Department of Oral Maxillofacial Surgery The University of Texas Health Science Center at Houston-
Descrição: dc.descriptionDepartment of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (Unesp)-
Descrição: dc.descriptionDepartment of Chemistry Rice University-
Descrição: dc.descriptionDepartment of Bioengineering Rice University-
Descrição: dc.descriptionTranslational Research Center Department of Oral and Maxillofacial Surgery New York University College of Dentistry-
Descrição: dc.descriptionNYU Pain Research Center Department of Molecular Pathobiology New York University College of Dentistry-
Descrição: dc.descriptionDepartment of Preventive and Restorative Sciences School of Dental Medicine University of Pennsylvania-
Descrição: dc.descriptionDepartment of Materials Science and Engineering School of Engineering & Applied Science University of Pennsylvania-
Descrição: dc.descriptionDepartment of Otolaryngology University of Alabama at Birmingham-
Descrição: dc.descriptionDepartment of Pediatrics Pennsylvania State University College of Medicine, Hershey-
Descrição: dc.descriptionDepartment of Biosciences and Oral Diagnosis Institute of Science and Technology São Paulo State University (Unesp)-
Idioma: dc.languageen-
Relação: dc.relationBiomedicines-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectanti-cancer-
Palavras-chave: dc.subjectantinociceptive effect-
Palavras-chave: dc.subjectOSCC-
Palavras-chave: dc.subjectSTINGel-
Título: dc.titleStimulator of Interferon Genes Pathway Activation through the Controlled Release of STINGel Mediates Analgesia and Anti-Cancer Effects in Oral Squamous Cell Carcinoma-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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