Studies on immunity and cancer in the human oral mucosa

Abstract

The immune system in the human oral mucosa is understudied compared to other barrier tissues, both in health and disease. The main aim of this thesis was to add new knowledge of the components of the oral immune cell compartment. The first part of the project revealed a striking heterogeneity of healthy oral mucosa antigen presenting cells (APCs) based on a single cell RNA sequence databank. This included 4 subsets of Langerhans cells (LCs). With their key role in linking innate and adaptive immunity, dysregulation of these cells may cause disease. In the second part of the project, the origin of LCs in oral mucosal biopsies from healthy persons and patients with the chronic inflammatory disease oral lichen planus (OLP) were studied using multicolor immunofluorescence. Increased numbers of LCs were detected in OLP biopsies compared with those in healthy oral mucosa. The increased cell numbers appeared to depend on recruited blood-derived dendritic cells (DCs). Moreover, such DCs gave rise to LC-like cells deeper in the mucosa of OLP lesions. In the third part of this project, expression of the transcription factor Krüppel-like factor 4 (KLF4) was examined in a Norwegian multicenter cohort of 128 malignant tumors of the tongue using immunohistochemistry. The results showed that the combination of high levels of KLF4 expression and a large inflammatory infiltrate in the tumors identified a group of patients with a significantly better prognosis than the rest of the patients. In vitro stimulations of cancer cell lines with the inflammatory cytokine interferon gamma caused upregulation of KLF4 in the cancer cells, suggesting a link between inflammation and KLF4 expression. The results aid to increase the understanding of diseases in the oral cavity and later develop improved management and targeted treatment.