Microbiome modulates immunotherapy response in cutaneous squamous cell carcinoma.

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.