Avaliação de macrófagos e suas citocinas IL-10, IL-12, IL-23, INF-γ e TGF-β em carcinoma espinocelular de cavidade oral
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Data
2012-08-21
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Universidade Federal de Goiás
Resumo
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-γ)
and anti-inflammatory (IL-10 and TGF-β) 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-β (10.8%) was
higher compared cytokines IL12/23/INF-γ (5.7%). Demonstrated although that a
high proportion of MA (CD11b+CD11c-) present in OCSCC expressed cytokines
IL-10, INF-γ and TGF-β compared to the control group, however this difference
was significant only for TGF-β (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-β, 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-β production.
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COSTA, Nádia do Lago. Tumor-associated macrophages and profile of inflamatory. 2012. 67 f. Tese (Doutorado em Ciencias da Saude) - Universidade Federal de Goiás, Goiânia, 2012.