title: Clinical relevance of the tumor microenvironment and immune escape of oral squamous cell carcinoma.
abstract: BACKGROUND
  Changes in the tumor microenvironment and immune surveillance represent crucial hallmarks of various kinds of cancer, including oral squamous cell carcinoma (OSCC), and a close crosstalk of hypoxia regulating genes, an activation of chemokines and immune cells has been described.
  
  
  METHODS
  A review about the pivotal role of HIF-1, its crosstalk to various cornerstones in OSCC tumorigenesis is presented.
  
  
  RESULTS
  Hypoxia is a frequent event in OSCC and leads to a reprogramming of the cellular metabolism in order to prevent cell death. Hypoxic OSCC cells induce different adaptive changes such as anaerobic glycolysis, pH stabilisation and alterations of the gene and protein expression profile. This complex metabolic program is orchestrated by the hypoxia inducible factor (HIF)-1, the master regulator of early tumor progression. Hypoxia-dependent and -independent alterations in immune surveillance lead to different immune evasion strategies, which are partially mediated by alterations of the tumor cells, changes in the frequency, activity and repertoire of immune cell infiltrates and of soluble and environmental factors of the tumor micromilieu with consecutive generation of an immune escape phenotype, progression of disease and poor clinical outcome of OSCC patients.
  
  
  CONCLUSIONS
  This review focusses on the importance of HIF-1 in the adaption and reprogramming of the metabolic system to reduced oxygen values as well as on the role of the tumor microenvironment for evasion of OSCC from immune recognition and destruction.
authors.affiliation: Department of Oral and Maxillofacial Plastic Surgery, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany. aw.eckert.wissenschaft@web.de.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Eckert
authors.affiliation: Institute of Pathology, Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 8, 06110, Halle (Saale), Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wickenhauser
authors.affiliation: Mazumdar Shaw Cancer Center and Narayana Hrudayalaya Multi Specialty Hospital, 258/A, Bommasandra Industrial Area, Bangalore, 560099, India.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Salins
authors.affiliation: Department of Oral and Maxillofacial Plastic Surgery, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.affiliation: Institute of Medical Immunology, Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 2, 06110, Halle (Saale), Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Bukur
authors.affiliation: Institute of Medical Immunology, Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 2, 06110, Halle (Saale), Germany. barbara.seliger@uk-halle.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Seliger
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D057131:Immune Evasion; D009062:Mouth Neoplasms / Q000276:immunology* / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor
keywords: Hypoxia; Immune escape; Immune response; Metabolic adaption; Oral squamous cell carcinoma