FOXP3型
免疫抑制
肿瘤微环境
CD8型
免疫系统
免疫学
生物
医学
癌症研究
作者
Maria Kosmidis,Piotr Dziunycz,Mayte Suárez‐Fariñas,Beda Mühleisen,Leo Schärer,Severin Läuchli,Jürg Hafner,Lars E. French,Carsten B. Schmidt‐Weber,John A. Carucci,Günther F.L. Hofbauer
出处
期刊:Journal of Immunotherapy
[Ovid Technologies (Wolters Kluwer)]
日期:2010-06-01
卷期号:33 (5): 538-546
被引量:37
标识
DOI:10.1097/cji.0b013e3181cc2615
摘要
In Brief 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-γ, IL-4, TGF-β, 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-γ 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-β 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. Supplemental Digital Content is available in the article
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