Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development
Abstract 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 te...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-04-01
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| Series: | Oncogenesis |
| Online Access: | https://doi.org/10.1038/s41389-024-00513-6 |
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| _version_ | 1823861593196199936 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Joshua K. Stone |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-cdfd8b5885b44df59ed98c80eee47052 |
| institution | Kabale University |
| issn | 2157-9024 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Oncogenesis |
| spelling | doaj-art-cdfd8b5885b44df59ed98c80eee470522025-02-09T12:54:48ZengNature Publishing GroupOncogenesis2157-90242024-04-0113111610.1038/s41389-024-00513-6Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma developmentJoshua K. Stone0Natalia von Muhlinen1Chenran Zhang2Ana I. Robles3Amy L. Flis4Eleazar Vega-Valle5Akihiko Miyanaga6Masaru Matsumoto7K. Leigh Greathouse8Tomer Cooks9Giorgio Trinchieri10Curtis C. Harris11Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory Animal Science Program, Laboratory of Human Carcinogenesis, Leidos Biomedical Research, Frederick National Laboratory for Cancer ResearchLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteHuman Science and Design, Robbins College of Health and Human Sciences, Baylor UniversityThe Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the NegevLaboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer InstituteLaboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer InstituteAbstract 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.https://doi.org/10.1038/s41389-024-00513-6 |
| spellingShingle | 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 Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development Oncogenesis |
| title | Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development |
| title_full | Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development |
| title_fullStr | Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development |
| title_full_unstemmed | Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development |
| title_short | Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development |
| title_sort | acidovorax temperans skews neutrophil maturation and polarizes th17 cells to promote lung adenocarcinoma development |
| url | https://doi.org/10.1038/s41389-024-00513-6 |
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