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Updated: Jul 16, 2025
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Bifidobacterium affects antitumor efficacy of oncolytic adenovirus in a mouse model of melanoma
Lorella Tripodi1,2, Sara Feola3, Ilaria Granata4
1CEINGE Biotecnologie Avanzate Franco Salvatore s.c.a.r.l, Napoli, Italy.
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.
Insights
The gut microbiome influences cancer immunotherapy effectiveness. Supplementing with Bifidobacterium enhanced oncolytic adenovirus therapy in melanoma models by modulating the immune response.
Area of Science:
- Oncology
- Immunology
- Microbiology
Background:
- Gut microbiota significantly impacts cancer immunotherapy outcomes, particularly in melanoma.
- Oncolytic viruses (OVs) are promising cancer therapeutics that induce immunogenic cancer cell death (ICD) and recruit immune cells.
Purpose of the Study:
- To investigate the role of gut microbiota in mediating the anti-tumor activity of oncolytic adenovirus Ad5D24-CpG (Ad-CpG).
- To explore the potential of microbial modulation to enhance Ad-CpG efficacy in melanoma treatment.
Main Methods:
- Utilized a syngeneic mouse model of melanoma.
- Perturbed gut microbiota using vancomycin and supplemented with Bifidobacterium.
- Assessed tumor progression, ICD, and immune cell infiltration (including regulatory T cells).
- Analyzed fecal microbiota composition.
Main Results:
- Vancomycin-induced gut microbiota disruption weakened Ad-CpG-mediated ICD.
- Oral Bifidobacterium supplementation enhanced Ad-CpG efficacy, reducing melanoma progression and tumor-infiltrating regulatory T cells.
- Fecal microbiota in mice treated with Bifidobacterium and Ad-CpG showed enrichment in Firmicutes.
Conclusions:
- The anti-tumor activity of Ad-CpG is significantly modulated by the gut microbiota.
- Bifidobacterium supplementation can enhance oncolytic adenovirus therapy in melanoma.
- Molecular mimicry between bacterial epitopes and tumor antigens may be a mechanism driving microbiota-mediated enhancement of OV response.
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