Distinct Innate Immune Gene Expression Profiles in Non-Melanoma Skin Cancer of Immunocompetent and Immunosuppressed Patients

Amanda Ewart Toland,Beda Muehleisen,Shang Brian Jiang,Richard L. Gallo,Tissa Hata,Monika Gerber,Julie A. Gladsjo

doi:10.1371/journal.pone.0040754

Abstract

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most frequent skin cancers in humans. An intact immune system is critical for protection against SCC since organ transplant recipients (OTR) have a 60- to 100-fold higher risk for developing these tumors. The role of the innate immune system in tumor immunosurveillance is unclear. Our aim was to determine the expression of selected innate immune genes in BCC and SCC arising in immunocompetent and OTR patients. Lesional and peri-lesional skin from 28 SCC and 19 BCC were evaluated for mRNA expression of toll-like receptors (TLR) 1–9, downstream TLR signaling molecules, and antimicrobial peptides. 11 SCC occurring in OTR patients were included in the analysis. We found that SCC but not BCC showed significantly elevated expression of TLRs 1–3, 5–8, TRIF and TRAF1. TNF was increased in SCC compared to normal skin. BCC showed increased IFNγ. hBD1, hBD2 and psoriasin mRNA and protein expression were significantly higher in SCC than in normal skin and higher than in BCC. SCC from OTR showed only an increase in hBD2 but no increase in hBD1 or psoriasin. We conclude that innate immune gene expression in SCC is distinct from normal skin and BCC. BCC shows lesser induction of innate immune genes. SCC from OTR patients have depressed expression of hBD1 and psoriasin compared to SCC from immunocompetent patients.

Highlights

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent non-melanoma skin cancers (NMSC) in humans [1]
We found that SCC but not basal cell carcinoma (BCC) showed significantly elevated expression of toll-like receptors (TLR) 1–3, 5–8, TRIF and TRAF1
SCCs came from 17 immunocompetent patients and 11 that were organ transplant recipients (OTR)

Summary

Introduction

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequent non-melanoma skin cancers (NMSC) in humans [1]. Significant progress has been made in understanding the pathogenesis of NMSC, the host immune defense mechanisms that predict patient outcome are still largely unknown. The highly increased incidence of skin cancers in immunosuppressed patients such as organ transplant recipients (OTRs) [4] has clearly shown the importance of the immune system in controlling the development of NMSC. Most research on tumor immunosurveillance in NMSC, including those within the framework of cancer immunoediting [7,8], have focused mainly on T-cell mediated, adaptive immune mechanisms. There is evidence that innate immune mechanisms are important in NMSC. Recognition of microbes results in expression of antimicrobial peptides (AMPs), cytokines and chemokines [11,12,13,14,15]

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