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
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.