Avaliação de macrófagos e suas citocinas IL-10, IL-12, IL-23, INF-γ e TGF-β em carcinoma espinocelular de cavidade oral

• Ano de defesa: 2012
• Autor(a) principal: COSTA, Nádia do Lago
• Orientador(a): BATISTA, Aline Carvalho
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Doutorado em Ciencias da Saude
• Departamento: Ciencias da Saude
• País: BR
• Palavras-chave em Português: Câncer de boca; carcinoma espinocelular; macrófagos; citocinas inflamatórias
• Palavras-chave em Inglês: Oral câncer; squamous cell carcinoma; macrophages
• Área do conhecimento CNPq: CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tde/1547

Tumor-Associated Macrophages (TAMs) can contribute with events involved in the progression and in the invasion of the tumor (angiogenesis, degradation of the extracellular matrix and local immunosuppression), or collaborate with an effective antitumor response and reduce the progression and metastasis. The purpose of these studies was to evaluate the macrophages (MA) presence in the microenvironment of oral cavity squamous cell carcinoma (OCSCC), and the relationship of these cells with clinicopathological factors. Additionally, we aimed also to characterize these cells through the expression of pro (IL-12/23 e INF-&#947;) and anti-inflammatory (IL-10 and TGF-&#946;) by macrophages and globally in selected samples. Besides that, considering these goals, the techniques of immunohistochemistry, flow cytometry and qRT-PCR were used. The results revealed, even with the flow cytometry technique, that a predominance of M2 phenotype macrophage in the tumor microenviromment of OCSCC, because the proportion of macrophages expressed both cytokines IL-10/TGF-&#946; (10.8%) was higher compared cytokines IL12/23/INF-&#947; (5.7%). Demonstrated although that a high proportion of MA (CD11b+CD11c-) present in OCSCC expressed cytokines IL-10, INF-&#947; and TGF-&#946; compared to the control group, however this difference was significant only for TGF-&#946; (Mann Whitney; P = 0,016). The evaluation of the expression of messenger RNA (mRNA) by qRT-PCR technique revealed a high overall expression of cytokines TGF-&#946;, IL-10 and IL-23 in OCSCC in metastatic when compared with control (P < 0,05 for all groups). The proportion of macrophages (CD68+), identified by immunohistochemistry technique, was significantly lower in the control group (normal oral mucosa) when compared to OCSCC groups with and without cervical lymph node metastasis (Mann Whitney; P = 0,00001 e P = 0,044, respectively). Additionally, the proportion of these cells was significantly higher in metastatic OCSCC when compared with non-metastatic (Mann Whitney; P = 0,038). Survival analysis showed that patients with a high proportion of CD68+ cells showed a trend toward shorter survival (44 months) than those with low proportion of these cells (93 months) (Kaplan-Meier; Log Rank, P = 0,08). In conclusion, the results suggest that there is a predominance of the M2 phenotype on the microenviromment of OCSCCC. Additionally, these cells may promote metastasis and reduce survival of patients affected by OCSCC, probably contributing to a local immunosuppression via TGF-&#946; production.