Oral Mucosal Langerhans Cells in Tumor Microenvironment – Enemy or Friends?

Introduction: Langerhans cells (LCs) are highly potent antigen-presenting-cells (APCs) exclusively residing in stratified epithelia of the skin and mucosae. LCs can be characterized by their anatomical location as well as by high expression of Langerin (CD207) and epithelial-cell-adhesion-molecule (EpCAM). We recently discovered the unique origin of oral LCs (OLC) and their developmental mechanisms during steady state and inflammatory conditions. With regards to their function, LCs play a critical role in maintaining oral homeostasis and preventing pathological consequences. Oral SCC is one of the most common malignancies. Though major changes in diagnostic and therapeutic techniques occurred, survival rates have not improved over last decades, and still remain below 50%. Locoregional recurrence has critical role in the poor prognosis. Hence, further understanding of tumor development and identifying risk factors is of supreme importance in optimizing diagnosis and therapy. A relationship between LCs and prognosis has been published in different tumors raising the question of whether LCs have a role in the immunosurveillance against cancer. However, there are only a few reports investigating this relationship in the context of oral SCC.

Objectives: Clarify the clinical significance of OLC in carcinoma of the tongue

Methods: 108 patients were examined and clinicopathological parameters were collected. Immunohistochemistry staining, qRT-PCR and flow cytometry analysis were performed on frozen biopsy or healthy fresh tissues to assess distribution and location of OLC and other molecules which play a role in the development and maturation of LCs.

Results: 23 patients with locoregional recurrence were diagnosed. Disease-specific-survival was 61%. Number of OLC significantly correlated with staging and differentiation of the tumors. Furthermore, OLC quantification predicts the prognosis and recurrence. Interestingly distribution of OLC as well as the expression level and localization of TGFβ highly correlated to the depth of the tumor invasion.

Conclusion: Our study reports an association between OLC and tumor progression. In addition, we suggest OLC as a predictive factor for prognosis and locoregional recurrence in carcinoma of the tongue.