title: Role of tumour-associated macrophages in oral squamous cells carcinoma progression: an update on current knowledge.
abstract: BACKGROUND
  Oral squamous cell carcinoma (OSCC) accounts over 90% of malignant neoplasms of the oral cavity. This pathological entity is associated to a high mortality rate that has remained unchanged over the past decades. Tumour-associated macrophages (TAMs) are believed to have potential involvement in OSCC progression. However, the molecular networks involved in communication between stroma and cancer cells have not yet been fully elucidated.
  
  
  METHODS
  The role of M2 polarized cells in oral carcinogenesis is supported by a correlation between TAMs accumulation into OSCC stroma and poor clinical outcome. Signalling pathways such as the NF-κB and cytokines released in the tumour microenvironment promote a bidirectional cross-talk between M2 and OSCC cells. These interactions consequently result in an increased proliferation of malignant cells and enhances aggressiveness, thus reducing patients' survival time.
  
  
  CONCLUSIONS
  Here, we present a comprehensive review of the role of interleukin (IL)-1, IL-4, IL-6, IL-8, IL-10 and the receptor tyrosine kinase Axl in macrophage polarization to an M2 phenotype and OSCC progression. Understanding the molecular basis of oral carcinogenesis and metastatic spread of OSCC would promote the development of targeted treatment contributing to a more favourable prognosis.
authors.affiliation: Postgraduate Program in Dentistry, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. maria.petruzzi@acad.pucrs.br.|Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690 - Ipiranga, Porto Alegre, RS, CEP: 90610-000, Brazil. maria.petruzzi@acad.pucrs.br.
authors.forename: Maria Noel Marzano Rodrigues
authors.initials: MN
authors.lastname: Petruzzi
authors.affiliation: Postgraduate Program in Dentistry, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.|Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690 - Ipiranga, Porto Alegre, RS, CEP: 90610-000, Brazil.
authors.forename: Karen
authors.initials: K
authors.lastname: Cherubini
authors.affiliation: Postgraduate Program in Dentistry, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.|Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690 - Ipiranga, Porto Alegre, RS, CEP: 90610-000, Brazil.
authors.forename: Fernanda Gonçalves
authors.initials: FG
authors.lastname: Salum
authors.affiliation: Postgraduate Program in Dentistry, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.|Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Av. Ipiranga, 6690 - Ipiranga, Porto Alegre, RS, CEP: 90610-000, Brazil.
authors.forename: Maria Antonia Zancanaro
authors.initials: MA
authors.lastname: de Figueiredo
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D018450:Disease Progression; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009062:Mouth Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D059016:Tumor Microenvironment; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D007378:Interleukins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: Head and neck cancer; Macrophage activation; Oral cancer; Oral squamous cell carcinoma