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.
Bifidobacterium affects antitumor efficacy of oncolytic adenovirus in a mouse model of melanoma / Tripodi, L.; Feola, S.; Granata, I.; Whalley, T.; Passariello, M.; Capasso, C.; Coluccino, L.; Vitale, M.; Scalia, G.; Gentile, L.; De Lorenzo, C.; Guarracino, M. R.; Castaldo, G.; D'Argenio, V.; Szomolay, B.; Cerullo, V.; Pastore, L.. - In: ISCIENCE. - ISSN 2589-0042. - 26:10(2023), p. 107668. [10.1016/j.isci.2023.107668]
Bifidobacterium affects antitumor efficacy of oncolytic adenovirus in a mouse model of melanoma
Tripodi L.Primo
Membro del Collaboration Group
;Feola S.;Passariello M.;Coluccino L.;Vitale M.;Scalia G.;De Lorenzo C.;Castaldo G.;D'Argenio V.;Cerullo V.
;Pastore L.
2023
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.File | Dimensione | Formato | |
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