Clinical relevance of the tumor microenvironment and immune escape of oral squamous cell carcinoma

被引:95
作者
Eckert, Alexander W. [1 ]
Wickenhauser, Claudia [3 ]
Salins, Paul C. [4 ,5 ]
Kappler, Matthias [1 ]
Bukur, Juergen [2 ]
Seliger, Barbara [2 ]
机构
[1] Univ Halle Wittenberg, Dept Oral & Maxillofacial Plast Surg, Ernst Grube Str 40, D-06120 Halle, Saale, Germany
[2] Univ Halle Wittenberg, Inst Med Immunol, Magdeburger Str 2, D-06120 Halle, Saale, Germany
[3] Univ Halle Wittenberg, Inst Pathol, Magdeburger Str 8, D-06110 Halle, Saale, Germany
[4] Mazumdar Shaw Canc Ctr, 258-A Bommasandra Ind Area, Bangalore 560099, Karnataka, India
[5] Narayana Hrudayalaya Multi Specialty Hosp, 258-A Bommasandra Ind Area, Bangalore 560099, Karnataka, India
关键词
Oral squamous cell carcinoma; Hypoxia; Metabolic adaption; Immune escape; Immune response; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; REGULATORY T-CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; CLASS-I ANTIGEN; PLURIPOTENCY FACTOR NANOG; ENDOTHELIAL GROWTH-FACTOR; TOLL-LIKE RECEPTORS; PERIPHERAL-BLOOD; DENDRITIC CELLS; CANCER-CELLS;
D O I
10.1186/s12967-016-0828-6
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
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.
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页数:13
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