Bifidobacterium affects antitumor efficacy of oncolytic adenovirus in a mouse model of melanoma

Tripodi, Lorella, Feola, Sara, Granata, Ilaria, Whalley, Thomas, Passariello, Margherita, Capasso, Cristian, Coluccino, Ludovica, Vitale, Maria, Scalia, Giulia, Gentile, Laura, De Lorenzo, Claudia, Guarracino, Mario Rosario, Castaldo, Giuseppe, D?Argenio, Valeria, Szomolay, Barbara ORCID: https://orcid.org/0000-0002-5375-5533, Cerullo, Vincenzo and Pastore, Lucio 2023. Bifidobacterium affects antitumor efficacy of oncolytic adenovirus in a mouse model of melanoma. iScience 26 (10) , 107668. 10.1016/j.isci.2023.107668

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Abstract

Gut microbiota plays a key role in modulating responses to cancer immunotherapy in melanoma patients. Oncolytic viruses (OVs) represent emerging tools in cancer therapy, inducing a potent immunogenic cancer cell death (ICD) and recruiting immune cells in tumors, poorly infiltrated by T cells. We investigated whether the antitumoral activity of oncolytic adenovirus Ad5D24-CpG (Ad-CpG) was gut microbiota-mediated in a syngeneic mouse model of melanoma and observed that ICD was weakened by vancomycin-mediated perturbation of gut microbiota. Ad-CpG efficacy was increased by oral supplementation with Bifidobacterium, reducing melanoma progression and tumor-infiltrating regulatory T cells. Fecal microbiota was enriched in bacterial species belonging to the Firmicutes phylum in mice treated with both Bifidobacterium and Ad-CpG; furthermore, our data suggest that molecular mimicry between melanoma and Bifidobacterium-derived epitopes may favor activation of cross-reactive T cells and constitutes one of the mechanisms by which gut microbiota modulates OVs response.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	Cell Press
ISSN:	2589-0042
Date of First Compliant Deposit:	5 October 2023
Date of Acceptance:	16 August 2023
Last Modified:	07 Oct 2023 22:39
URI:	https://orca.cardiff.ac.uk/id/eprint/162989

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