Distinct innate immune gene expression profiles in non-melanoma skin cancer of immunocompetent and immunosuppressed patients.
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.
Division of Dermatology, University of California San Diego, La Jolla, California, United States of America.
Beda
B
Muehleisen
Shang Brian
SB
Jiang
Julie A
JA
Gladsjo
Monika
M
Gerber
Tissa
T
Hata
Richard L
RL
Gallo
D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004817:Epidermis / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007121:Immunocompetence / Q000235:genetics* / Q000276:immunology; D016867:Immunocompromised Host / Q000235:genetics* / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000276:immunology; D016377:Organ Transplantation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D012333:RNA, Messenger; D051193:Toll-Like Receptors