Joshua K. Stone, Natalia von Muhlinen, Chenran Zhang, Ana I. Robles, Amy L. Flis, Eleazar Vega-Valle, Akihiko Miyanaga, Masaru Matsumoto, K. Leigh Greathouse, Tomer Cooks, Giorgio Trinchieri, Curtis C. Harris
{"title":"嗜酸性粒细胞扭曲了中性粒细胞的成熟并使Th17细胞极化,从而促进了肺腺癌的发展","authors":"Joshua K. Stone, Natalia von Muhlinen, Chenran Zhang, Ana I. Robles, Amy L. Flis, Eleazar Vega-Valle, Akihiko Miyanaga, Masaru Matsumoto, K. Leigh Greathouse, Tomer Cooks, Giorgio Trinchieri, Curtis C. Harris","doi":"10.1038/s41389-024-00513-6","DOIUrl":null,"url":null,"abstract":"<p>Change within the intratumoral microbiome is a common feature in lung and other cancers and may influence inflammation and immunity in the tumor microenvironment, affecting growth and metastases. We previously characterized the lung cancer microbiome in patients and identified <i>Acidovorax temperans</i> as enriched in tumors. Here, we instilled <i>A. temperans</i> in an animal model driven by mutant K-ras and Tp53. This revealed <i>A. temperans</i> accelerates tumor development and burden through infiltration of proinflammatory cells. Neutrophils exposed to <i>A. temperans</i> displayed a mature, pro-tumorigenic phenotype with increased cytokine signaling, with a global shift away from IL-1β signaling. Neutrophil to monocyte and macrophage signaling upregulated MHC II to activate CD4<sup>+</sup> T cells, polarizing them to an IL-17A<sup>+</sup> phenotype detectable in CD4<sup>+</sup> and γδ populations (T17). These T17 cells shared a common gene expression program predictive of poor survival in human LUAD. These data indicate bacterial exposure promotes tumor growth by modulating inflammation.</p><figure></figure>","PeriodicalId":19489,"journal":{"name":"Oncogenesis","volume":"53 1","pages":""},"PeriodicalIF":5.9000,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development\",\"authors\":\"Joshua K. Stone, Natalia von Muhlinen, Chenran Zhang, Ana I. Robles, Amy L. Flis, Eleazar Vega-Valle, Akihiko Miyanaga, Masaru Matsumoto, K. Leigh Greathouse, Tomer Cooks, Giorgio Trinchieri, Curtis C. Harris\",\"doi\":\"10.1038/s41389-024-00513-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Change within the intratumoral microbiome is a common feature in lung and other cancers and may influence inflammation and immunity in the tumor microenvironment, affecting growth and metastases. We previously characterized the lung cancer microbiome in patients and identified <i>Acidovorax temperans</i> as enriched in tumors. Here, we instilled <i>A. temperans</i> in an animal model driven by mutant K-ras and Tp53. This revealed <i>A. temperans</i> accelerates tumor development and burden through infiltration of proinflammatory cells. Neutrophils exposed to <i>A. temperans</i> displayed a mature, pro-tumorigenic phenotype with increased cytokine signaling, with a global shift away from IL-1β signaling. Neutrophil to monocyte and macrophage signaling upregulated MHC II to activate CD4<sup>+</sup> T cells, polarizing them to an IL-17A<sup>+</sup> phenotype detectable in CD4<sup>+</sup> and γδ populations (T17). These T17 cells shared a common gene expression program predictive of poor survival in human LUAD. These data indicate bacterial exposure promotes tumor growth by modulating inflammation.</p><figure></figure>\",\"PeriodicalId\":19489,\"journal\":{\"name\":\"Oncogenesis\",\"volume\":\"53 1\",\"pages\":\"\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-04-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oncogenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41389-024-00513-6\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncogenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41389-024-00513-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development
Change within the intratumoral microbiome is a common feature in lung and other cancers and may influence inflammation and immunity in the tumor microenvironment, affecting growth and metastases. We previously characterized the lung cancer microbiome in patients and identified Acidovorax temperans as enriched in tumors. Here, we instilled A. temperans in an animal model driven by mutant K-ras and Tp53. This revealed A. temperans accelerates tumor development and burden through infiltration of proinflammatory cells. Neutrophils exposed to A. temperans displayed a mature, pro-tumorigenic phenotype with increased cytokine signaling, with a global shift away from IL-1β signaling. Neutrophil to monocyte and macrophage signaling upregulated MHC II to activate CD4+ T cells, polarizing them to an IL-17A+ phenotype detectable in CD4+ and γδ populations (T17). These T17 cells shared a common gene expression program predictive of poor survival in human LUAD. These data indicate bacterial exposure promotes tumor growth by modulating inflammation.
期刊介绍:
Oncogenesis is a peer-reviewed open access online journal that publishes full-length papers, reviews, and short communications exploring the molecular basis of cancer and related phenomena. It seeks to promote diverse and integrated areas of molecular biology, cell biology, oncology, and genetics.