Commensal <i>Bifidobacterium</i> Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines

A large body of data both in animals and humans demonstrates that the gut microbiome plays a fundamental role in cancer immunity and in determining the efficacy of cancer immunotherapy. In this work, we have investigated whether and to what extent the gut microbiome can influence the antitumor activ...

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Main Authors: Michele Tomasi, Mattia Dalsass, Francesco Beghini, Ilaria Zanella, Elena Caproni, Laura Fantappiè, Assunta Gagliardi, Carmela Irene, Enrico König, Luca Frattini, Giulia Masetti, Samine Jessica Isaac, Federica Armanini, Fabio Cumbo, Aitor Blanco-Míguez, Alberto Grandi, Nicola Segata, Guido Grandi
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/9/11/1356
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author Michele Tomasi
Mattia Dalsass
Francesco Beghini
Ilaria Zanella
Elena Caproni
Laura Fantappiè
Assunta Gagliardi
Carmela Irene
Enrico König
Luca Frattini
Giulia Masetti
Samine Jessica Isaac
Federica Armanini
Fabio Cumbo
Aitor Blanco-Míguez
Alberto Grandi
Nicola Segata
Guido Grandi
author_facet Michele Tomasi
Mattia Dalsass
Francesco Beghini
Ilaria Zanella
Elena Caproni
Laura Fantappiè
Assunta Gagliardi
Carmela Irene
Enrico König
Luca Frattini
Giulia Masetti
Samine Jessica Isaac
Federica Armanini
Fabio Cumbo
Aitor Blanco-Míguez
Alberto Grandi
Nicola Segata
Guido Grandi
author_sort Michele Tomasi
collection DOAJ
description A large body of data both in animals and humans demonstrates that the gut microbiome plays a fundamental role in cancer immunity and in determining the efficacy of cancer immunotherapy. In this work, we have investigated whether and to what extent the gut microbiome can influence the antitumor activity of neo-epitope-based cancer vaccines in a BALB/c-CT26 cancer mouse model. Similarly to that observed in the C57BL/6-B16 model, <i>Bifidobacterium</i> administration per se has a beneficial effect on CT26 tumor inhibition. Furthermore, the combination of <i>Bifidobacterium</i> administration and vaccination resulted in a protection which was superior to vaccination alone and to <i>Bifidobacterium</i> administration alone, and correlated with an increase in the frequency of vaccine-specific T cells. The gut microbiome analysis by 16S rRNA gene sequencing and shotgun metagenomics showed that tumor challenge rapidly altered the microbiome population, with <i>Muribaculaceae</i> being enriched and <i>Lachnospiraceae</i> being reduced. Over time, the population of <i>Muribaculaceae</i> progressively reduced while the <i>Lachnospiraceae</i> population increased—a trend that appeared to be retarded by the oral administration of <i>Bifidobacterium</i>. Interestingly, in some <i>Bacteroidales</i>, <i>Prevotella</i> and <i>Muribaculacee</i> species we identified sequences highly homologous to immunogenic neo-epitopes of CT26 cells, supporting the possible role of “molecular mimicry” in anticancer immunity. Our data strengthen the importance of the microbiome in cancer immunity and suggests a microbiome-based strategy to potentiate neo-epitope-based cancer vaccines.
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spelling doaj.art-123201bff12b4c2b9b6af5be9639b8222023-11-23T01:53:41ZengMDPI AGVaccines2076-393X2021-11-01911135610.3390/vaccines9111356Commensal <i>Bifidobacterium</i> Strains Enhance the Efficacy of Neo-Epitope Based Cancer VaccinesMichele Tomasi0Mattia Dalsass1Francesco Beghini2Ilaria Zanella3Elena Caproni4Laura Fantappiè5Assunta Gagliardi6Carmela Irene7Enrico König8Luca Frattini9Giulia Masetti10Samine Jessica Isaac11Federica Armanini12Fabio Cumbo13Aitor Blanco-Míguez14Alberto Grandi15Nicola Segata16Guido Grandi17Department of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyToscana Life Sciences, 53100 Siena, ItalyToscana Life Sciences, 53100 Siena, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyToscana Life Sciences, 53100 Siena, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyDepartment of Cellular, Computational and Integrative Biology, University of Trento, 38123 Trento, ItalyA large body of data both in animals and humans demonstrates that the gut microbiome plays a fundamental role in cancer immunity and in determining the efficacy of cancer immunotherapy. In this work, we have investigated whether and to what extent the gut microbiome can influence the antitumor activity of neo-epitope-based cancer vaccines in a BALB/c-CT26 cancer mouse model. Similarly to that observed in the C57BL/6-B16 model, <i>Bifidobacterium</i> administration per se has a beneficial effect on CT26 tumor inhibition. Furthermore, the combination of <i>Bifidobacterium</i> administration and vaccination resulted in a protection which was superior to vaccination alone and to <i>Bifidobacterium</i> administration alone, and correlated with an increase in the frequency of vaccine-specific T cells. The gut microbiome analysis by 16S rRNA gene sequencing and shotgun metagenomics showed that tumor challenge rapidly altered the microbiome population, with <i>Muribaculaceae</i> being enriched and <i>Lachnospiraceae</i> being reduced. Over time, the population of <i>Muribaculaceae</i> progressively reduced while the <i>Lachnospiraceae</i> population increased—a trend that appeared to be retarded by the oral administration of <i>Bifidobacterium</i>. Interestingly, in some <i>Bacteroidales</i>, <i>Prevotella</i> and <i>Muribaculacee</i> species we identified sequences highly homologous to immunogenic neo-epitopes of CT26 cells, supporting the possible role of “molecular mimicry” in anticancer immunity. Our data strengthen the importance of the microbiome in cancer immunity and suggests a microbiome-based strategy to potentiate neo-epitope-based cancer vaccines.https://www.mdpi.com/2076-393X/9/11/1356cancer vaccinesmicrobiomeimmunotherapyOMVspersonalized medicine
spellingShingle Michele Tomasi
Mattia Dalsass
Francesco Beghini
Ilaria Zanella
Elena Caproni
Laura Fantappiè
Assunta Gagliardi
Carmela Irene
Enrico König
Luca Frattini
Giulia Masetti
Samine Jessica Isaac
Federica Armanini
Fabio Cumbo
Aitor Blanco-Míguez
Alberto Grandi
Nicola Segata
Guido Grandi
Commensal <i>Bifidobacterium</i> Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines
Vaccines
cancer vaccines
microbiome
immunotherapy
OMVs
personalized medicine
title Commensal <i>Bifidobacterium</i> Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines
title_full Commensal <i>Bifidobacterium</i> Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines
title_fullStr Commensal <i>Bifidobacterium</i> Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines
title_full_unstemmed Commensal <i>Bifidobacterium</i> Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines
title_short Commensal <i>Bifidobacterium</i> Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines
title_sort commensal i bifidobacterium i strains enhance the efficacy of neo epitope based cancer vaccines
topic cancer vaccines
microbiome
immunotherapy
OMVs
personalized medicine
url https://www.mdpi.com/2076-393X/9/11/1356
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