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
Affiliations
Lorella Tripodi
CEINGE Biotecnologie Avanzate Franco Salvatore s.c.a.r.l, Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy
Sara Feola
Drug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland
Ilaria Granata
Institute for High-Performance Computing and Networking National Research Council Branch of Naples, 509066 Naples, Naples, Italy
Thomas Whalley
School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK
Margherita Passariello
CEINGE Biotecnologie Avanzate Franco Salvatore s.c.a.r.l, Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy
Cristian Capasso
Drug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland
Ludovica Coluccino
CEINGE Biotecnologie Avanzate Franco Salvatore s.c.a.r.l, Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy
CEINGE Biotecnologie Avanzate Franco Salvatore s.c.a.r.l, Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy
Mario Rosario Guarracino
University of Cassino and Southern Lazio Department of Economics and Law, 154984 Cassino, Frosinone, Italy
Giuseppe Castaldo
CEINGE Biotecnologie Avanzate Franco Salvatore s.c.a.r.l, Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy
Valeria D’Argenio
CEINGE Biotecnologie Avanzate Franco Salvatore s.c.a.r.l, Napoli, Italy; Department of Human Sciences and Quality of Life Promotion, San Raffaele Open University, Rome, Italy
Barbara Szomolay
Division of Infection and Immunity and Systems Immunity Research Institute, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, UK
Vincenzo Cerullo
Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy; Drug Research Program (DRP), ImmunoViroTherapy Lab (IVT), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, 00790 Helsinki, Finland; Corresponding author
Lucio Pastore
CEINGE Biotecnologie Avanzate Franco Salvatore s.c.a.r.l, Napoli, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy; Corresponding author
Summary: 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.
