The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment
Abstract Background A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vu...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-023-04113-7 |
| _version_ | 1797836303489826816 |
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| author | Natalia Rustetska Magdalena Szczepaniak Krzysztof Goryca Elwira Bakuła-Zalewska Małgorzata Figat Artur Kowalik Stanisław Góźdź Magdalena Kowalewska |
| author_facet | Natalia Rustetska Magdalena Szczepaniak Krzysztof Goryca Elwira Bakuła-Zalewska Małgorzata Figat Artur Kowalik Stanisław Góźdź Magdalena Kowalewska |
| author_sort | Natalia Rustetska |
| collection | DOAJ |
| description | Abstract Background A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression. Methods Clinical material was obtained from 89 patients with VSCC. Next-generation sequencing (NGS) of 16S rRNA and quantitative polymerase chain reaction (qPCR) were used to detect bacterial species in VSCC. To verify neutrophil activation, CD66b expression in tumour specimens was analysed by immunohistochemistry (IHC). Subsequently, IHC was applied to detect the main neutrophil serine proteases (NSPs), cathepsin G (CTSG), neutrophil elastase (ELANE), and proteinase 3 (PRTN3) in VSCC. Results Fusobacterium nucleatum and Pseudomonas aeruginosa were identified as tumour-promoting bacteria, and their presence was found to be associated with a shorter time to progression in VSCC patients. Furthermore, high abundance of CD66b, the neutrophil activation marker, in VSCC samples, was found to relate to poor survival of patients with VSCC. The selected NSPs were shown to be expressed in vulvar tumours, also within microabscess. The increased numbers of microabscesess were correlated with poor survival in VSCC patients. Conclusions Our results show that neutrophilic inflammation seem to be permissive for tumour-promoting bacteria growth in VSCC. The findings provide new therapeutic opportunities, such as based on shifting the balance of neutrophil populations to those with antitumorigenic activity and on targeting NSPs produced by activated neutrophils at the inflammation sites. |
| first_indexed | 2024-04-09T15:07:45Z |
| format | Article |
| id | doaj.art-b1bf2e75028a45208291d11b71d2a0c6 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-09T15:07:45Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-b1bf2e75028a45208291d11b71d2a0c62023-04-30T11:26:31ZengBMCJournal of Translational Medicine1479-58762023-04-0121111110.1186/s12967-023-04113-7The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironmentNatalia Rustetska0Magdalena Szczepaniak1Krzysztof Goryca2Elwira Bakuła-Zalewska3Małgorzata Figat4Artur Kowalik5Stanisław Góźdź6Magdalena Kowalewska7Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of OncologyDepartment of Molecular Diagnostics, Holycross Cancer CentreGenomics Core Facility, Centre of New Technologies, University of WarsawDepartment of Pathology, Maria Sklodowska-Curie National Research Institute of OncologyDepartment of Gynecologic Oncology, Maria Sklodowska-Curie National Research Institute of OncologyDepartment of Molecular Diagnostics, Holycross Cancer CentreDepartment of Clinical Oncology, Holycross Cancer CentreDepartment of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of OncologyAbstract Background A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression. Methods Clinical material was obtained from 89 patients with VSCC. Next-generation sequencing (NGS) of 16S rRNA and quantitative polymerase chain reaction (qPCR) were used to detect bacterial species in VSCC. To verify neutrophil activation, CD66b expression in tumour specimens was analysed by immunohistochemistry (IHC). Subsequently, IHC was applied to detect the main neutrophil serine proteases (NSPs), cathepsin G (CTSG), neutrophil elastase (ELANE), and proteinase 3 (PRTN3) in VSCC. Results Fusobacterium nucleatum and Pseudomonas aeruginosa were identified as tumour-promoting bacteria, and their presence was found to be associated with a shorter time to progression in VSCC patients. Furthermore, high abundance of CD66b, the neutrophil activation marker, in VSCC samples, was found to relate to poor survival of patients with VSCC. The selected NSPs were shown to be expressed in vulvar tumours, also within microabscess. The increased numbers of microabscesess were correlated with poor survival in VSCC patients. Conclusions Our results show that neutrophilic inflammation seem to be permissive for tumour-promoting bacteria growth in VSCC. The findings provide new therapeutic opportunities, such as based on shifting the balance of neutrophil populations to those with antitumorigenic activity and on targeting NSPs produced by activated neutrophils at the inflammation sites.https://doi.org/10.1186/s12967-023-04113-7Vulvar carcinomaMicrobiotaFusobacterium nucleatumPseudomonas aeruginosaNeutrophil serine proteaseMicroabscess |
| spellingShingle | Natalia Rustetska Magdalena Szczepaniak Krzysztof Goryca Elwira Bakuła-Zalewska Małgorzata Figat Artur Kowalik Stanisław Góźdź Magdalena Kowalewska The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment Journal of Translational Medicine Vulvar carcinoma Microbiota Fusobacterium nucleatum Pseudomonas aeruginosa Neutrophil serine protease Microabscess |
| title | The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment |
| title_full | The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment |
| title_fullStr | The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment |
| title_full_unstemmed | The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment |
| title_short | The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment |
| title_sort | intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment |
| topic | Vulvar carcinoma Microbiota Fusobacterium nucleatum Pseudomonas aeruginosa Neutrophil serine protease Microabscess |
| url | https://doi.org/10.1186/s12967-023-04113-7 |
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