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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Microbiome modulates immunotherapy response in cutaneous squamous cell carcinoma
Abstract:
The gut microbiome is increasingly recognized to alter cancer risk, progression, and response to treatments such as immunotherapy, especially in cutaneous melanoma. However, whether the microbiome influences immune checkpoint inhibitor (ICI) immunotherapy response to non-melanoma skin cancer has not yet been defined. As squamous cell carcinomas (SCC) are in closest proximity to the skin microbiome, we hypothesized that the skin microbiome, which regulates cutaneous immunity, might affect SCC-associated anti-PD1 immunotherapy treatment response. We used ultraviolet radiation to induce SCC in SKH1 hairless mice. We then treated the mice with broad-band antibiotics to deplete the microbiome, followed by colonization by candidate skin and gut bacteria or persistent antibiotic treatment, all in parallel with ICI treatment. We longitudinally monitored skin and gut microbiome dynamics by 16S rRNA gene sequencing, and tumor burden by periodic tumor measurements and histologic assessment. Our study revealed that antibiotics-induced abrogation of the microbiome reduced tumor burden, suggesting a functional role of the microbiome in non-melanoma skin cancer therapy response.
Insights
The skin microbiome impacts non-melanoma skin cancer (NMSC) treatment. Depleting the microbiome with antibiotics reduced tumor burden in mice receiving immunotherapy, indicating its role in NMSC therapy response.
Area of Science:
- Microbiology
- Immunology
- Dermatology
Background:
- The gut microbiome influences cancer progression and immunotherapy response, particularly in melanoma.
- The role of the microbiome in non-melanoma skin cancer (NMSC) response to immune checkpoint inhibitors (ICIs) remains undefined.
- Squamous cell carcinomas (SCC) are closely associated with the skin microbiome, suggesting a potential influence on cutaneous immunity and anti-PD1 therapy.
Approach:
- SCC was induced in SKH1 hairless mice using ultraviolet radiation.
- Mice were treated with antibiotics to deplete the microbiome, followed by bacterial colonization or sustained antibiotic treatment during ICI therapy.
- Skin and gut microbiome dynamics were monitored using 16S rRNA gene sequencing, alongside tumor burden assessment via measurements and histology.
Key Points:
- Antibiotic-induced microbiome depletion led to reduced tumor burden in mice with SCC.
- The study highlights a functional link between the skin microbiome and anti-PD1 immunotherapy efficacy in NMSC.
- Microbiome modulation presents a potential therapeutic strategy for enhancing NMSC treatment outcomes.
Conclusions:
- The skin microbiome plays a significant role in the response to anti-PD1 immunotherapy for non-melanoma skin cancer.
- Abrogating the microbiome through antibiotics demonstrated a therapeutic benefit in reducing tumor burden.
- Further research into microbiome-targeted interventions could improve NMSC treatment efficacy.
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