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Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance
Non-conventional T cells, such as γδ T and invariant natural killer T (iNKT) cells, are emerging players in fighting cancer. Alpha-galactosylceramide (α-GalCer) is used as an exogenous ligand to activate iNKT cells. Human cells don’t have a direct pathway producing α-GalCer, which, however, can be p...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180740/ https://www.ncbi.nlm.nih.gov/pubmed/35682578 http://dx.doi.org/10.3390/ijms23115896 |
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author | Ustjanzew, Arsenij Sencio, Valentin Trottein, François Faber, Jörg Sandhoff, Roger Paret, Claudia |
author_facet | Ustjanzew, Arsenij Sencio, Valentin Trottein, François Faber, Jörg Sandhoff, Roger Paret, Claudia |
author_sort | Ustjanzew, Arsenij |
collection | PubMed |
description | Non-conventional T cells, such as γδ T and invariant natural killer T (iNKT) cells, are emerging players in fighting cancer. Alpha-galactosylceramide (α-GalCer) is used as an exogenous ligand to activate iNKT cells. Human cells don’t have a direct pathway producing α-GalCer, which, however, can be produced by bacteria. We searched the literature for bacteria strains that are able to produce α-GalCer and used available sequencing data to analyze their presence in human tumor tissues and their association with survival. The modulatory effect of antibiotics on the concentration of α-GalCer was analyzed in mice. The human gut bacteria Bacteroides fragilis, Bacteroides vulgatus, and Prevotella copri produce α-GalCer structures that are able to activate iNKT cells. In mice, α-GalCer was depleted upon treatment with vancomycin. The three species were detected in colon adenocarcinoma (COAD) and rectum adenocarcinoma tissues, and Prevotella copri was also detected in bone tumors and glioblastoma tissues. Bacteroides vulgatus in COAD tissues correlated with better survival. In conclusion, α-GalCer-producing bacteria are part of the human gut microbiome and can infiltrate tumor tissues. These results suggest a new mechanism of interaction between bacteria and immune cells: α-GalCer produced by bacteria may activate non-conventional T cells in tumor tissues, where they can exert a direct or indirect anti-tumor activity. |
format | Online Article Text |
id | pubmed-9180740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91807402022-06-10 Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance Ustjanzew, Arsenij Sencio, Valentin Trottein, François Faber, Jörg Sandhoff, Roger Paret, Claudia Int J Mol Sci Article Non-conventional T cells, such as γδ T and invariant natural killer T (iNKT) cells, are emerging players in fighting cancer. Alpha-galactosylceramide (α-GalCer) is used as an exogenous ligand to activate iNKT cells. Human cells don’t have a direct pathway producing α-GalCer, which, however, can be produced by bacteria. We searched the literature for bacteria strains that are able to produce α-GalCer and used available sequencing data to analyze their presence in human tumor tissues and their association with survival. The modulatory effect of antibiotics on the concentration of α-GalCer was analyzed in mice. The human gut bacteria Bacteroides fragilis, Bacteroides vulgatus, and Prevotella copri produce α-GalCer structures that are able to activate iNKT cells. In mice, α-GalCer was depleted upon treatment with vancomycin. The three species were detected in colon adenocarcinoma (COAD) and rectum adenocarcinoma tissues, and Prevotella copri was also detected in bone tumors and glioblastoma tissues. Bacteroides vulgatus in COAD tissues correlated with better survival. In conclusion, α-GalCer-producing bacteria are part of the human gut microbiome and can infiltrate tumor tissues. These results suggest a new mechanism of interaction between bacteria and immune cells: α-GalCer produced by bacteria may activate non-conventional T cells in tumor tissues, where they can exert a direct or indirect anti-tumor activity. MDPI 2022-05-24 /pmc/articles/PMC9180740/ /pubmed/35682578 http://dx.doi.org/10.3390/ijms23115896 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ustjanzew, Arsenij Sencio, Valentin Trottein, François Faber, Jörg Sandhoff, Roger Paret, Claudia Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance |
title | Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance |
title_full | Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance |
title_fullStr | Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance |
title_full_unstemmed | Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance |
title_short | Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance |
title_sort | interaction between bacteria and the immune system for cancer immunotherapy: the α-galcer alliance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180740/ https://www.ncbi.nlm.nih.gov/pubmed/35682578 http://dx.doi.org/10.3390/ijms23115896 |
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