Costa, Nadia LagoValadares, Marize CamposSouza, Pedro Paulo Chaves [UNESP]Mendonça, Elismauro FranciscoOliveira, José CarlosSilva, Tarcíla AparecidaBatista, Aline Carvalho2014-05-272014-05-272013-03-01Oral Oncology, v. 49, n. 3, p. 216-223, 2013.1368-83751879-0593http://hdl.handle.net/11449/74683Objective: To evaluate and characterize macrophage populations (M1/M2) in the tumor microenvironment of oral cavity squamous cell carcinoma (OCSCC). The relationship between macrophages and clinicopathological factors, such as survival data, lymph node metastasis, tumoral proliferation, and WHO histological grading are also analyzed. Materials and methods: The samples consisted of surgically excised specimens from patients with non-metastatic and metastatic OCSCC and normal oral mucosa (control). Immunohistochemistry, flow cytometry, and qRT-PCR were used to evaluate macrophage populations and the expression of pro- (IL-12, IL-23, and INF-γ) and anti-inflammatory (IL-10 and TGF-β) cytokines. The level required for statistical significance was defined as p < 0.05. Results: The data showed a predominance of M2 phenotype (high percentage of IL-10+TGF-β+) macrophages in the tumor microenvironment of OCSCC. A higher percentage of macrophages expressing TGF-β was seen in the OCSCC group when compared with healthy individuals. The assessment of mRNA expression also presented a greater expression of anti-inflammatory cytokines TGFβ and IL10 in OCSCC when compared with the control group. The percentage of macrophages, demonstrated by immunohistochemistry, was significantly higher in the metastatic OCSCC group than in the non-metastatic and control groups. The log-rank test also showed that the mean survival time for patients with high levels of macrophages was less (44 months) when compared with patients with a low percentage of such cells (93 months). Conclusion: A predominance of the M2 phenotype in the tumor microenvironment of OCSCC could contribute to local immunosuppression, via TGF-β production, and consequently greater lymph node involvement and reduced patient survival time. © 2012 Elsevier Ltd. All rights reserved.216-223engCytokinesInterferon-gammaInterleukin-10Interleukin-12Interleukin-23MacrophagesOral cancerSquamous cell carcinomaTransforming growth factor betagamma interferoninterleukin 10interleukin 12interleukin 23messenger RNAtransforming growth factor betaadultagedcancer invasioncancer stagingcancer survivalcell populationcell proliferationcontrolled studycytokine releasefemaleflow cytometryhistopathologyhumanhuman cellhuman tissueimmunohistochemistrylymph node metastasismacrophagemajor clinical studymalemouth mucosamouth squamous cell carcinomanucleotide sequencephenotypepriority journalretrospective studyreverse transcription polymerase chain reactionsurvival timetumor associated leukocytetumor localizationtumor microenvironmenttumor volumeAdultAgedAged, 80 and overAntigens, CD11Carcinoma, Squamous CellCell CountCell ProliferationFemaleFollow-Up StudiesHumansImmune ToleranceInflammation MediatorsLymphatic MetastasisMaleMiddle AgedMouth NeoplasmsNeoplasm GradingNeoplasm InvasivenessRetrospective StudiesSurvival RateTransforming Growth Factor betaTumor MicroenvironmentArtigo10.1016/j.oraloncology.2012.09.012WOS:000314871900011Acesso restrito2-s2.0-84873412294