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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	cancer vaccines microbiome immunotherapy OMVs personalized medicine Medicine R
Acceso en línea:	https://doaj.org/article/123201bff12b4c2b9b6af5be9639b822
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spelling	oai:doaj.org-article:123201bff12b4c2b9b6af5be9639b8222021-11-25T19:11:35ZCommensal <i>Bifidobacterium</i> Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines10.3390/vaccines91113562076-393Xhttps://doaj.org/article/123201bff12b4c2b9b6af5be9639b8222021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1356https://doaj.org/toc/2076-393XA 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.Michele TomasiMattia DalsassFrancesco BeghiniIlaria ZanellaElena CaproniLaura FantappièAssunta GagliardiCarmela IreneEnrico KönigLuca FrattiniGiulia MasettiSamine Jessica IsaacFederica ArmaniniFabio CumboAitor Blanco-MíguezAlberto GrandiNicola SegataGuido GrandiMDPI AGarticlecancer vaccinesmicrobiomeimmunotherapyOMVspersonalized medicineMedicineRENVaccines, Vol 9, Iss 1356, p 1356 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	cancer vaccines microbiome immunotherapy OMVs personalized medicine Medicine R
spellingShingle	cancer vaccines microbiome immunotherapy OMVs personalized medicine Medicine R 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
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.
format	article
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
title	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_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_sort	commensal <i>bifidobacterium</i> strains enhance the efficacy of neo-epitope based cancer vaccines
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/123201bff12b4c2b9b6af5be9639b822
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Commensal <i>Bifidobacterium</i> Strains Enhance the Efficacy of Neo-Epitope Based Cancer Vaccines

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