Microbiome modulates immunotherapy response in cutaneous squamous cell carcinoma
Document Type
Article
Publication Date
10-2023
Original Citation
Voigt A,
Walter A,
Young T,
Graham J,
Batista Bittencourt BM,
de Mingo Pulido A,
Prieto K,
Tsai KY,
Sundberg J,
Oh J.
Microbiome modulates immunotherapy response in cutaneous squamous cell carcinoma Exp Dermatol. 2023;32(10):1624-32.
Keywords
JGM, JMG, SS1
JAX Source
Exp Dermatol. 2023;32(10):1624-32.
PMID
37350109
DOI
https://doi.org/10.1111/exd.14864
Grant
American Cancer Society; LEO Pharma Research Foundation; National Institutes of Health; Pyewacket PostDoc Fund; Scott R. MacKenzie Foundation
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.