Immunosuppression Affects CD4+ mRNA Expression and Induces Th2 Dominance in the Microenvironment of Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients

Abstract

Squamous cell carcinoma (SCC) is the most frequent cancer in organ transplant recipients (OTRs). The immune system plays a major role in the fight against SCC, however, little is known about the local inflammatory response in SCC at all. We analyzed quantity and quality of the perineoplastic inflammatory SCC microenvironment in immunocompetent patients and immmunosuppressed OTRs. RNA expression profile of SCC patients was analyzed for 8 different sets of genes relating to Th1 versus Th2 response using Gene Set Enrichment Analysis. SCC from immunocompetent patients and OTRs were analyzed by real-time polymerase chain reactions for CD4, CD8, TBET, GATA-3, FOXP3, RORC, IFN-gamma, IL-4, TGF-beta, IL-10, and IL-17A mRNA expression. Immunohistochemistry was carried out in SCC for CD3, CD4, CD8, and FOXP3 expression. Considerable inflammation was seen in both patient groups. SCC in immunocompetent patients and OTRs was associated with a mixed Th1 and Th2 gene expression signature. CD4(+) mRNA was diminished in immunosuppression. Skin adjacent to SCC in OTRs showed Th2 expression pattern as compared with immunocompetent patients. T-BET and IFN-gamma mRNA expression were decreased in the OTR group. Although Th17-weighted inflammation was unchanged, IL-17A mRNA level was markedly decreased with immunosuppression. Regulatory T cells, characterized by FOX-P3 and TGF-beta mRNA level, were decreased in OTRs. Our findings support the hypothesis that nontumor-bearing skin adjacent to SCC in OTRs is not necessarily normal and that the local microenvironment may contribute to a field effect contributing to higher recurrence rates and more aggressive behavior observed in these patients.

The Distribution of CD8- and Foxp3-positive T Cells in Skin Squamous Cell Tumors and Basal Cell Carcinomas

“…Previous studies showing that MHC class I expression and CD8 positive T cell infiltration were significantly lower in BCC than in SCC support our current result about the numerical difference of infiltrating CD8 positive T cells among BCC, BD and SCC [3,23]. Tregs infiltration was previously observed in BCC and SCC [12,15]. In those studies, the authors found that Tregs infiltration was associated with the TH2 dominant microenvironment.…”

Skin Cancer in Organ Transplant Recipients

“…Expression of cytokeratins (especially CK 5/6), p63 and CAM5.2 is particularly helpful for proving the epithelial origin of spindle cell SCC. Perineural growth appears not to be more frequent in OTR, but it indicates more extensive growth and a higher risk of recurrence [4,8,9]. The peritumoral inflammatory infiltrate is significantly less intense in OTR [4].…”

Lectures = Vortraege

“…In conclusion, our study provides biomarkers of endogenous skin ageing in both females and males, which are not dependent on gender, and therefore, on the different hormone status. 1,12,7 SD 9,7 (p < 0,03),24,7 SD 15,6 (p = 0,2),46,9 SD 34,5 (p = 0,6 …”