title: Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Stomatology (Oral Pathology), Dental School, Federal University of Goiás, Goiânia, Brazil. nadialago@hotmail.com
authors.forename: Nadia Lago
authors.initials: NL
authors.lastname: Costa
authors.forename: Marize Campos
authors.initials: MC
authors.lastname: Valadares
authors.forename: Pedro Paulo Chaves
authors.initials: PP
authors.lastname: Souza
authors.forename: Elismauro Francisco
authors.initials: EF
authors.lastname: Mendonça
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Oliveira
authors.forename: Tarcíla Aparecida
authors.initials: TA
authors.lastname: Silva
authors.forename: Aline Carvalho
authors.initials: AC
authors.lastname: Batista
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018845:CD11 Antigens / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000556:secondary; D002452:Cell Count; D049109:Cell Proliferation; D016207:Cytokines / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D018836:Inflammation Mediators / Q000032:analysis*; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D053759:Interleukin-23 / Q000032:analysis; D008207:Lymphatic Metastasis / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000145:classification / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000276:immunology* / Q000473:pathology; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000032:analysis; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D018845:CD11 Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D053759:Interleukin-23; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma