Skin Microbiome Variation with Cancer Progression in Human Cutaneous Squamous Cell Carcinoma.

Authors

Anita Y Voigt, The Jackson LaboratoryFollow
Akintunde Emiola, The Jackson LaboratoryFollow
Jethro Johnson, The Jackson LaboratoryFollow
Elizabeth Fleming, The Jackson LaboratoryFollow
Hoan Nguyen, The Jackson LaboratoryFollow
Wei Zhou, The Jackson LaboratoryFollow
Kenneth Y Tsai
Christine Fink
Julia Oh, The Jackson LaboratoryFollow

Document Type

Article

Publication Date

10-1-2022

Publication Title

The Journal of investigative dermatology

Keywords

Anti-Bacterial Agents, Carcinoma, Squamous Cell, Humans, Keratosis, Actinic, Microbiota, Skin Neoplasms

JAX Source

J Invest Dermatol . 2022 Oct;142(10):2773-2782.e16.

Volume

142

Issue

10

First Page

2773

Last Page

2782

ISSN

1523-1747

PMID

35390349

DOI

10.1016/j.jid.2022.03.017

Grant

We are thankful to the JO group for inspiring discussions and acknowledge the contribution of the Genome Technologies Service at The Jackson Labo- ratory for expert assistance with sample sequencing for the work described in this publication. We are grateful to George W. Weinstock, Jennifer C. Chen, Paul Igor Costea, Luis Sordo Veira, and Parithi Balachandran for helpful dis- cussions. This work was funded by the American Cancer Society (RSG-16- 255-01-MPC and IRG-82-003-33 NCCC-01), the LEO Foundation, the JAX Cancer Center grant (P30 CA03419), the Scott R. MacKenzie Foundation, and the Mark Foundation for Cancer Research. JO is additionally supported by the National Institutes of Health (1 R01 AR078634-01, DP2 GM126893-01, and K22 AI119231-01; 1U54NS105539; 1 U19 AI142733; and 1 R21 AR075174). We are grateful for the funding of AYV through the Pyewacket PostDoc Fund.

Abstract

The skin microbiome plays a critical role in skin homeostasis and disorders. UVR is the major cause of nonmelanoma skin cancer, but other risk factors, including immune suppression, chronic inflammation, and antibiotic usage, suggest the microbiome as an additional, unexplored risk factor and potential disease biomarker. The overarching goal was to study the skin microbiome in squamous cell carcinoma (SCC) and premalignant actinic keratosis compared with that in healthy skin to identify skin cancer‒associated changes in the skin microbiome. We performed a high-resolution analysis of shotgun metagenomes of actinic keratosis and SCC in healthy skin, revealing the microbial community shifts specific to actinic keratosis and SCC. Most prominently, the relative abundance of pathobiont Staphylococcus aureus was increased at the expense of commensal Cutibacterium acnes in SCC compared with that in healthy skin, and enrichment of functional pathways in SCC reflected this shift. Notably, C. acnes associated with lesional versus healthy skin differed at the strain level, suggesting the specific functional changes associated with its depletion in SCC. Our study revealed a transitional microbial dysbiosis from healthy skin to actinic keratosis to SCC, supporting further investigation of the skin microbiome for use as a biomarker and providing hypotheses for studies investigating how these microbes might influence skin cancer progression.

Recommended Citation

Voigt A, Emiola A, Johnson J, Fleming E, Nguyen H, Zhou W, Tsai K, Fink C, Oh J. Skin Microbiome Variation with Cancer Progression in Human Cutaneous Squamous Cell Carcinoma. J Invest Dermatol . 2022 Oct;142(10):2773-2782.e16.