Progression of cutaneous squamous cell carcinoma in immunosuppressed patients is associated with reduced CD123+ and FOXP3+ cells in the perineoplastic inflammatory infiltrate.

AIMS Squamous cell carcinoma of the skin (SCC) increases dramatically in organ transplant recipients (OTRs). The aim was to determine whether qualitative and quantitative differences in perineoplastic inflammation in OTRs contribute to the increased carcinogenesis. METHODS AND RESULTS We studied the perineoplastic inflammatory infiltrate in SCC, assessing depth, density and phenotype (CD3, 4, 8, FOXP3, CD123 and STAT1) by immunohistochemistry in paired biopsy specimens of intraepithelial and invasive SCC in immunocompetent patients and OTRs. Considerable inflammation was observed in all intraepithelial SCC (inflammatory infiltrate depth 2.80 +/- 2.21 mm immunocompetent patients, 2.15 +/- 2.95 mm OTRs). Inflammation was more pronounced in invasive SCC of immunocompetent patients (4.60 +/- 4.67 mm) and OTRs (3.30 +/- 5.90 mm) (P < 0.005). The density of perineoplastic inflammatory infiltrates increased from intraepithelial to invasive SCC (P = 0.005). OTRs showed a lower density of perineoplastic inflammatory infiltrate (P = 0.041). OTRs also showed reduced CD3+ T-lymphocyte and CD8+ cytotoxic T-lymphocyte proportions in intraepithelial SCC (P = 0.025 and 0.027, respectively). FOXP3+ regulatory T-lymphocyte proportions in OTRs' invasive SCC were markedly diminished (P = 0.048). CD123+ plasmacytoid dendritic cells increased in the progression from intraepithelial to invasive SCC in immunocompetent patients (P = 0.040). CD123+ cells were reduced in all SCC of OTRs (P = 0.036). CONCLUSIONS Perineoplastic inflammation in intraepithelial SCC is pronounced both in immunocompetent patients and OTRs. Inflammation increases further in invasive SCC. OTRs show reduced proportions of FOXP3+ regulatory T cells and CD123+ plasmacytoid dendritic cells. This distinct inflammatory infiltrate may result in increased cutaneous carcinogenesis and more aggressive behaviour of SCC in OTRs.