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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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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
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author Zhu, Chao
Li, Jiang
Yao, Mianfeng
Fang, Changyun
author_facet Zhu, Chao
Li, Jiang
Yao, Mianfeng
Fang, Changyun
author_sort Zhu, Chao
collection PubMed
description 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.
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spelling pubmed-85015662021-10-20 Potential for treatment benefit of STING agonists plus immune checkpoint inhibitors in oral squamous cell carcinoma Zhu, Chao Li, Jiang Yao, Mianfeng Fang, Changyun BMC Oral Health Research 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. BioMed Central 2021-10-08 /pmc/articles/PMC8501566/ /pubmed/34625078 http://dx.doi.org/10.1186/s12903-021-01813-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhu, Chao
Li, Jiang
Yao, Mianfeng
Fang, Changyun
Potential for treatment benefit of STING agonists plus immune checkpoint inhibitors in oral squamous cell carcinoma
title Potential for treatment benefit of STING agonists plus immune checkpoint inhibitors in oral squamous cell carcinoma
title_full Potential for treatment benefit of STING agonists plus immune checkpoint inhibitors in oral squamous cell carcinoma
title_fullStr Potential for treatment benefit of STING agonists plus immune checkpoint inhibitors in oral squamous cell carcinoma
title_full_unstemmed Potential for treatment benefit of STING agonists plus immune checkpoint inhibitors in oral squamous cell carcinoma
title_short Potential for treatment benefit of STING agonists plus immune checkpoint inhibitors in oral squamous cell carcinoma
title_sort potential for treatment benefit of sting agonists plus immune checkpoint inhibitors in oral squamous cell carcinoma
topic Research
url 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
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