Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment
Abstract Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially metastasizes. These effects are evident in CRC consensus molecular subtypes (CMS) where both CMS1 and CMS4 contain immune infiltra...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-023-00429-w |
| _version_ | 1797577738528227328 |
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| author | A. K. Sulit M. Daigneault E. Allen-Vercoe O. K. Silander B. Hock J. McKenzie J. Pearson F. A. Frizelle S. Schmeier R. Purcell |
| author_facet | A. K. Sulit M. Daigneault E. Allen-Vercoe O. K. Silander B. Hock J. McKenzie J. Pearson F. A. Frizelle S. Schmeier R. Purcell |
| author_sort | A. K. Sulit |
| collection | DOAJ |
| description | Abstract Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially metastasizes. These effects are evident in CRC consensus molecular subtypes (CMS) where both CMS1 and CMS4 contain immune infiltrates yet have opposing prognoses. The microbiome has previously been associated with CRC and immune response in CRC but has largely been ignored in the CRC subtype discussion. We used CMS subtyping on surgical resections from patients and aimed to determine the contributions of the microbiome to the pleiotropic effects evident in immune-infiltrated subtypes. We integrated host gene-expression and meta-transcriptomic data to determine the link between immune characteristics and microbiome contributions in these subtypes and identified lipopolysaccharide (LPS) binding as a potential functional mechanism. We identified candidate bacteria with LPS properties that could affect immune response, and tested the effects of their LPS on cytokine production of peripheral blood mononuclear cells (PBMCs). We focused on Fusobacterium periodonticum and Bacteroides fragilis in CMS1, and Porphyromonas asaccharolytica in CMS4. Treatment of PBMCs with LPS isolated from these bacteria showed that F. periodonticum stimulates cytokine production in PBMCs while both B. fragilis and P. asaccharolytica had an inhibitory effect. Furthermore, LPS from the latter two species can inhibit the immunogenic properties of F. periodonticum LPS when co-incubated with PBMCs. We propose that different microbes in the CRC tumor microenvironment can alter the local immune activity, with important implications for prognosis and treatment response. |
| first_indexed | 2024-03-10T22:13:13Z |
| format | Article |
| id | doaj.art-52d596d7788a489a85d7a1a9eec91535 |
| institution | Directory Open Access Journal |
| issn | 2055-5008 |
| language | English |
| last_indexed | 2024-03-10T22:13:13Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj.art-52d596d7788a489a85d7a1a9eec915352023-11-19T12:32:10ZengNature Portfolionpj Biofilms and Microbiomes2055-50082023-08-01911810.1038/s41522-023-00429-wBacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironmentA. K. Sulit0M. Daigneault1E. Allen-Vercoe2O. K. Silander3B. Hock4J. McKenzie5J. Pearson6F. A. Frizelle7S. Schmeier8R. Purcell9School of Natural Sciences, Massey UniversityDepartment of Molecular and Cellular Biology, University of GuelphDepartment of Molecular and Cellular Biology, University of GuelphSchool of Natural Sciences, Massey UniversityHaematology Research Group, University of OtagoHaematology Research Group, University of OtagoBiostatistics and Computational Biology Unit, University of OtagoDepartment of Surgery and Critical Care, University of OtagoSchool of Natural Sciences, Massey UniversityDepartment of Surgery and Critical Care, University of OtagoAbstract Immune responses can have opposing effects in colorectal cancer (CRC), the balance of which may determine whether a cancer regresses, progresses, or potentially metastasizes. These effects are evident in CRC consensus molecular subtypes (CMS) where both CMS1 and CMS4 contain immune infiltrates yet have opposing prognoses. The microbiome has previously been associated with CRC and immune response in CRC but has largely been ignored in the CRC subtype discussion. We used CMS subtyping on surgical resections from patients and aimed to determine the contributions of the microbiome to the pleiotropic effects evident in immune-infiltrated subtypes. We integrated host gene-expression and meta-transcriptomic data to determine the link between immune characteristics and microbiome contributions in these subtypes and identified lipopolysaccharide (LPS) binding as a potential functional mechanism. We identified candidate bacteria with LPS properties that could affect immune response, and tested the effects of their LPS on cytokine production of peripheral blood mononuclear cells (PBMCs). We focused on Fusobacterium periodonticum and Bacteroides fragilis in CMS1, and Porphyromonas asaccharolytica in CMS4. Treatment of PBMCs with LPS isolated from these bacteria showed that F. periodonticum stimulates cytokine production in PBMCs while both B. fragilis and P. asaccharolytica had an inhibitory effect. Furthermore, LPS from the latter two species can inhibit the immunogenic properties of F. periodonticum LPS when co-incubated with PBMCs. We propose that different microbes in the CRC tumor microenvironment can alter the local immune activity, with important implications for prognosis and treatment response.https://doi.org/10.1038/s41522-023-00429-w |
| spellingShingle | A. K. Sulit M. Daigneault E. Allen-Vercoe O. K. Silander B. Hock J. McKenzie J. Pearson F. A. Frizelle S. Schmeier R. Purcell Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment npj Biofilms and Microbiomes |
| title | Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment |
| title_full | Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment |
| title_fullStr | Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment |
| title_full_unstemmed | Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment |
| title_short | Bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment |
| title_sort | bacterial lipopolysaccharide modulates immune response in the colorectal tumor microenvironment |
| url | https://doi.org/10.1038/s41522-023-00429-w |
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