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J Immunother ; 33(5): 538-46, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20463594

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas/imunologia , Neoplasias Cutâneas/imunologia , Pele/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Idoso , Antígenos CD/biossíntese , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/etiologia , Citocinas/genética , Citocinas/metabolismo , Feminino , Fatores de Transcrição Forkhead/biossíntese , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Terapia de Imunossupressão/efeitos adversos , Interleucina-17/genética , Interleucina-17/metabolismo , Masculino , Transplante de Órgãos , Pele/imunologia , Pele/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/etiologia , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Linfócitos T Reguladores/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/imunologia , Fator de Crescimento Transformador beta/biossíntese
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