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

Lorella Tripodi; Sara Feola; Ilaria Granata; Thomas Whalley; Margherita Passariello; Cristian Capasso; Ludovica Coluccino; Maria Vitale; Giulia Scalia; Laura Gentile; Claudia De Lorenzo; Mario Rosario Guarracino; Giuseppe Castaldo; Valeria D'Argenio; Barbara Szomolay; Vincenzo Cerullo; Lucio Pastore

doi:10.1016/j.isci.2023.107668

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

iScience. 2023 Aug 19;26(10):107668. doi: 10.1016/j.isci.2023.107668. eCollection 2023 Oct 20.

Authors

Lorella Tripodi^{1

2}, Sara Feola³, Ilaria Granata⁴, Thomas Whalley⁵, Margherita Passariello^{1

2}, Cristian Capasso³, Ludovica Coluccino^{1

2}, Maria Vitale¹, Giulia Scalia¹, Laura Gentile¹, Claudia De Lorenzo^{1

2}, Mario Rosario Guarracino⁶, Giuseppe Castaldo^{1

2}, Valeria D'Argenio^{1

7}, Barbara Szomolay⁸, Vincenzo Cerullo^{2

3}, Lucio Pastore^{1

2}

Affiliations

¹ CEINGE Biotecnologie Avanzate Franco Salvatore s.c.a.r.l, Napoli, Italy.
² Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy.
³ Drug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland.
⁴ Institute for High-Performance Computing and Networking National Research Council Branch of Naples, 509066 Naples, Naples, Italy.
⁵ School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK.
⁶ University of Cassino and Southern Lazio Department of Economics and Law, 154984 Cassino, Frosinone, Italy.
⁷ Department of Human Sciences and Quality of Life Promotion, San Raffaele Open University, Rome, Italy.
⁸ Division of Infection and Immunity and Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, UK.

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.

Keywords: Cancer; Microbiome; Virology.