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Potential for treatment benefit of STING agonists plus immune checkpoint inhibitors in oral squamous cell carcinoma

BACKGROUND: DNA-sensing receptor cyclic GMP–AMP synthase (cGAS) and its downstream signaling effector stimulator of interferon genes (STING) present a novel role in anti-tumor immunity. Recently, the combination of cGAS-STING agonists and immunotherapy achieved promising results in some tumor types....

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Detalles Bibliográficos
Autores principales: Zhu, Chao, Li, Jiang, Yao, Mianfeng, Fang, Changyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501566/
https://www.ncbi.nlm.nih.gov/pubmed/34625078
http://dx.doi.org/10.1186/s12903-021-01813-8
Descripción
Sumario:BACKGROUND: DNA-sensing receptor cyclic GMP–AMP synthase (cGAS) and its downstream signaling effector stimulator of interferon genes (STING) present a novel role in anti-tumor immunity. Recently, the combination of cGAS-STING agonists and immunotherapy achieved promising results in some tumor types. The correlation between cGAS-STING signaling pathway and the tumor immune microenvironment in patients with oral squamous cell carcinoma (OSCC) is unclear. METHODS: We utilized RNA sequencing and clinical data of OSCC patients from the TCGA database to investigate the correlation between cGAS-STING signaling pathway and the tumor immune microenvironment. Six cGAS-STING related genes were obtained from previous studies to establish the enrichment score of cGAS-STING pathway. The differences in survival rate, immune cell infiltration, immune-related genes expression and immune-related biological pathways were studied in the cGAS-STING clusters. RESULTS: We observed a better prognosis of OSCC patients in the cGAS-STING high cluster. The infiltration ratio of immune cells and the expression profiles of immune-related genes were elevated when the cGAS-STING pathway is activated. The differentially expressed genes between high and low cGAS-STING clusters were enriched in immune-related biological pathways. CONCLUSIONS: Our findings suggest the potential benefit of combining STING agonists and immune checkpoint inhibitors in OSCC patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12903-021-01813-8.