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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
Anita Y Voigt1, Andrew Walter2, Timothy H Young2
1The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
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 colonisation 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 tumour burden by periodic tumour measurements and histologic assessment. Our study revealed that antibiotics-induced abrogation of the microbiome reduced the tumour 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, suggesting a key role in NMSC therapy response.
Area of Science:
- Microbiology
- Immunology
- Oncology
Background:
- The gut microbiome influences cancer progression and immunotherapy response, particularly in melanoma.
- The role of the microbiome in non-melanoma skin cancer (NMSC) immunotherapy response remains undefined.
- Squamous cell carcinoma (SCC) is closely associated with the skin microbiome, suggesting a potential influence on treatment outcomes.
Purpose of the Study:
- To investigate the impact of the skin microbiome on anti-PD1 immunotherapy response in NMSC.
- To determine if modulating the microbiome affects tumor burden in SCC models.
Main Methods:
- UV radiation was used to induce SCC in SKH1 hairless mice.
- Mice were treated with antibiotics to deplete the microbiome, followed by bacterial colonization or continued antibiotic treatment.
- Tumor burden and microbiome dynamics (16S rRNA sequencing) were monitored longitudinally during anti-PD1 immunotherapy.
Main Results:
- Antibiotic-induced microbiome depletion significantly reduced tumor burden in mice.
- Microbiome modulation influenced the response to anti-PD1 immunotherapy in this NMSC model.
Conclusions:
- The microbiome plays a functional role in NMSC therapy response.
- Targeting the skin microbiome may represent a novel therapeutic strategy for NMSC patients undergoing immunotherapy.
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