Changes in the skin microbiome associated with squamous cell carcinoma in transplant recipients

Seweryn Bialasiewicz,Ian H Frazer,Philip Hugenholtz,Sharon Gabizon,Mark Morrison,Julian Zaugg,Nancy Lachner,Priyamvada Sobarun,Lynlee L Lin,Annika Krueger,H Peter Soyer

doi:10.1038/s43705-022-00095-7

Abstract

Actinic keratoses (AK) arise in severely photo-damaged skin and can progress to squamous cell carcinomas (SCC). AK and SCC are common in Caucasian populations, and immunosuppressed individuals have a markedly higher risk of developing SCC. An overabundance of Staphylococcus aureus has been reported in AK and SCC lesions of immunocompetent individuals, however, the AK/SCC microbiome in immunosuppressed cohorts has not been investigated. Here, the microbial profile and bacterial load of AK, SCC and control skin swabs from 32 immunosuppressed organ transplant recipients were characterised via SSU rRNA gene sequencing and qPCR, and compared to a previously described immunocompetent cohort. Although the taxonomic composition of skin swab samples was mostly subject-specific, significant differences were observed between control skin, AK, and SCC in both cohorts. Surface bacterial load was increased and alpha diversity decreased in AK and SCC compared to control skin due to an increased abundance of Staphylococcus species and relative decrease of skin commensals. Staphylococcus epidermidis predominated on SCC from transplant recipients in contrast to SCC of immunocompetent subjects dominated by S. aureus. In conclusion, AK and SCC of immunosuppressed and immunocompetent subjects present with distinctive microbial dysbioses, which may be relevant to SCC pathogenesis and progression.

Highlights

Keratinocyte cancers are the most common cancer in Caucasian populations worldwide [1]
This study showed a reduction of commensal microorganisms, such as members of the genus Malassezia and Cutibacterium, and increase in relative abundance of S. aureus in actinic keratoses (AK) and squamous cell carcinomas (SCC) samples, compared to the control skin swabs [10]
Study cohorts and sample collection A total of 216 skin swabs were collected from a cohort of 32 organ transplant recipients who had been on immunosuppressive medication for at least one year (28 ≥ 5 years; 16 ≥ 15 years; see Supplementary Table S1 for detailed subject demographics)

Summary

Introduction

Keratinocyte cancers are the most common cancer in Caucasian populations worldwide [1]. Though squamous cell carcinomas (SCC) are a less prevalent type of keratinocyte cancer than basal cell carcinoma, SCC more commonly metastasise resulting in a greater mortality rate [2]. SCC typically arise from pre-malignant lesions termed actinic keratoses (AK). Individuals receiving immunosuppressive medication, including organ transplant recipients, have a higher prevalence of AK and SCC and an associated increased risk of metastasis and death [3, 4]. Other predominant risk factors include UV irradiation, advancing age, light skin colour and chronic inflammation [1]. An infectious aetiology has been suspected to play a role in skin malignancy [5,6,7]. Individuals with an impaired immune function are more susceptible to infection, which may increase their risk of microbially linked cancers [7]

Methods

Results

Conclusion