{"title":"核梭杆菌诱导肿瘤细胞内禀STING通路的激活与食管癌患者预后不良有关。","authors":"Shotaro Nakajima, Katsuharu Saito, Satoshi Fukai, Mei Sakuma, Akira Matsuishi, Ryo Kanoda, Yuya Maruyama, Hiroya Suzuki, Hirokazu Okayama, Motonobu Saito, Kosaku Mimura, Azuma Nirei, Tomohiro Kikuchi, Hiroyuki Hanayama, Zenichiro Saze, Tomoyuki Momma, Kyoko Nishiyama, Tatsuo Suzutani, Koji Kono","doi":"10.1007/s10388-025-01112-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Intratumoral Fusobacterium nucleatum (Fn) infection is closely associated with poor prognosis in esophageal cancer (EC) due to its impact on the tumor microenvironment (TME). The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical for regulating immune cell activation in the TME. However, the link between intratumoral Fn infection and the activation of the cGAS-STING pathway in tumor cells, as well as its effects on EC progression, remains largely unknown.</p><p><strong>Methods: </strong>In the present study, we investigated the impact of intratumoral Fn infection on the activation of the tumor cell-intrinsic cGAS-STING pathway and EC progression by analyzing our own EC cohort and performing in vitro experiments using co-cultures of EC-cell lines and Fn.</p><p><strong>Results: </strong>The expression of tumor cell-intrinsic STING was significantly associated with worse prognosis in Fn-high EC patients. Exposure to Fn significantly activated the STING pathway in EC cells. RNA-seq analysis revealed that exposure to Fn markedly activated cytokine-chemokine-related signaling pathways and induced the expression of several cytokines and chemokines in STING-expressing EC cells. Among the differentially expressed cytokine and chemokine genes in EC cells co-cultured with Fn, analysis of TCGA datasets demonstrated that the expression of CCL20, CXCL10, and CSF2 may be associated with poor prognosis in EC patients.</p><p><strong>Conclusion: </strong>We revealed that the activation of the STING signaling pathway and the subsequent expression of cytokines and chemokines in EC cells induced by Fn infection may be closely associated with poor prognosis in EC patients.</p>","PeriodicalId":11918,"journal":{"name":"Esophagus","volume":" ","pages":"239-249"},"PeriodicalIF":2.2000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Activation of the tumor cell-intrinsic STING pathway induced by Fusobacterium nucleatum is associated with poor prognosis in esophageal cancer patients.\",\"authors\":\"Shotaro Nakajima, Katsuharu Saito, Satoshi Fukai, Mei Sakuma, Akira Matsuishi, Ryo Kanoda, Yuya Maruyama, Hiroya Suzuki, Hirokazu Okayama, Motonobu Saito, Kosaku Mimura, Azuma Nirei, Tomohiro Kikuchi, Hiroyuki Hanayama, Zenichiro Saze, Tomoyuki Momma, Kyoko Nishiyama, Tatsuo Suzutani, Koji Kono\",\"doi\":\"10.1007/s10388-025-01112-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Intratumoral Fusobacterium nucleatum (Fn) infection is closely associated with poor prognosis in esophageal cancer (EC) due to its impact on the tumor microenvironment (TME). The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical for regulating immune cell activation in the TME. However, the link between intratumoral Fn infection and the activation of the cGAS-STING pathway in tumor cells, as well as its effects on EC progression, remains largely unknown.</p><p><strong>Methods: </strong>In the present study, we investigated the impact of intratumoral Fn infection on the activation of the tumor cell-intrinsic cGAS-STING pathway and EC progression by analyzing our own EC cohort and performing in vitro experiments using co-cultures of EC-cell lines and Fn.</p><p><strong>Results: </strong>The expression of tumor cell-intrinsic STING was significantly associated with worse prognosis in Fn-high EC patients. Exposure to Fn significantly activated the STING pathway in EC cells. RNA-seq analysis revealed that exposure to Fn markedly activated cytokine-chemokine-related signaling pathways and induced the expression of several cytokines and chemokines in STING-expressing EC cells. Among the differentially expressed cytokine and chemokine genes in EC cells co-cultured with Fn, analysis of TCGA datasets demonstrated that the expression of CCL20, CXCL10, and CSF2 may be associated with poor prognosis in EC patients.</p><p><strong>Conclusion: </strong>We revealed that the activation of the STING signaling pathway and the subsequent expression of cytokines and chemokines in EC cells induced by Fn infection may be closely associated with poor prognosis in EC patients.</p>\",\"PeriodicalId\":11918,\"journal\":{\"name\":\"Esophagus\",\"volume\":\" \",\"pages\":\"239-249\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Esophagus\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10388-025-01112-z\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Esophagus","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10388-025-01112-z","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/14 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
Activation of the tumor cell-intrinsic STING pathway induced by Fusobacterium nucleatum is associated with poor prognosis in esophageal cancer patients.
Background: Intratumoral Fusobacterium nucleatum (Fn) infection is closely associated with poor prognosis in esophageal cancer (EC) due to its impact on the tumor microenvironment (TME). The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical for regulating immune cell activation in the TME. However, the link between intratumoral Fn infection and the activation of the cGAS-STING pathway in tumor cells, as well as its effects on EC progression, remains largely unknown.
Methods: In the present study, we investigated the impact of intratumoral Fn infection on the activation of the tumor cell-intrinsic cGAS-STING pathway and EC progression by analyzing our own EC cohort and performing in vitro experiments using co-cultures of EC-cell lines and Fn.
Results: The expression of tumor cell-intrinsic STING was significantly associated with worse prognosis in Fn-high EC patients. Exposure to Fn significantly activated the STING pathway in EC cells. RNA-seq analysis revealed that exposure to Fn markedly activated cytokine-chemokine-related signaling pathways and induced the expression of several cytokines and chemokines in STING-expressing EC cells. Among the differentially expressed cytokine and chemokine genes in EC cells co-cultured with Fn, analysis of TCGA datasets demonstrated that the expression of CCL20, CXCL10, and CSF2 may be associated with poor prognosis in EC patients.
Conclusion: We revealed that the activation of the STING signaling pathway and the subsequent expression of cytokines and chemokines in EC cells induced by Fn infection may be closely associated with poor prognosis in EC patients.
期刊介绍:
Esophagus, the official journal of the Japan Esophageal Society, introduces practitioners and researchers to significant studies in the fields of benign and malignant diseases of the esophagus. The journal welcomes original articles, review articles, and short articles including technical notes ( How I do it ), which will be peer-reviewed by the editorial board. Letters to the editor are also welcome. Special articles on esophageal diseases will be provided by the editorial board, and proceedings of symposia and workshops will be included in special issues for the Annual Congress of the Society.