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Published on: February 3, 2023
Immune checkpoints indoleamine 2,3-dioxygenase 1 and programmed death-ligand 1 in oral mucosal dysplasia
Meri Sieviläinen1, Fabricio Passador-Santos2, Rabeia Almahmoudi1
1Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland.
Background:
Oral mucosal dysplasia is a histologic feature of potentially malignant disorders that is associated with the risk of transformation to carcinoma. Dysplastic cells use many strategies during their transformation to cancer, including escape from the immune mediated destruction. We hypothesized that adaptive immunity is inhibited by activation of distinct immune checkpoint molecules, such as indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1).
Methods:
We collected 63 oral dysplasia samples from 47 patients. Nine biopsies from alveolar mucosa were taken during wisdom teeth extractions were used as healthy controls. Tissue samples were stained and scored for IDO1 and PD-L1. Additionally, dysplasia grades and inflammatory cell infiltration were evaluated. Eight patients were followed up to 36 months to evaluate dysplasia progression, inflammation, and immune checkpoint molecules expression.
Results:
Dysplastic epithelium had significantly lower IDO1 expression than that of healthy controls. PD-L1 positive cells in the lamina propria were mainly in dysplastic samples and seldom in healthy controls. Dysplasia grade was associated negatively with epithelium IDO1 and positively with IDO1 and PD-L1 expression in the lamina propria. There was a positive association between dysplasia grade and level of inflammatory cell infiltration. During follow-up, dysplasia grade, inflammatory cell infiltration, and the immune checkpoint expression fluctuated over time.
Conclusions:
Immune checkpoint molecules IDO1 and PD-L1 are modulated during oral epithelial dysplastic changes, and their expression is associated with inflammatory cell infiltration in the lamina propria. As immune checkpoint molecules expression fluctuates over time, these molecules are not useful as biomarkers for oral mucosal dysplasia progression.
Insights
Immune checkpoints indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1) are modulated in oral dysplasia. Their expression fluctuates, making them unsuitable biomarkers for disease progression.
Area of Science:
- Oral pathology
- Immunology
- Cancer research
Background:
- Oral mucosal dysplasia is a precancerous condition.
- Dysplastic cells evade immune destruction.
- Immune checkpoints like IDO1 and PD-L1 may inhibit adaptive immunity.
Purpose of the Study:
- To investigate the expression and role of IDO1 and PD-L1 in oral dysplasia.
- To determine if these immune checkpoints are associated with dysplasia grade and inflammation.
- To evaluate their potential as biomarkers for oral dysplasia progression.
Main Methods:
- Analysis of 63 oral dysplasia and 9 healthy control samples.
- Staining and scoring for IDO1 and PD-L1 expression.
- Evaluation of dysplasia grade, inflammation, and immune checkpoint expression over 36 months.
Main Results:
- Dysplastic epithelium showed lower IDO1 expression than controls.
- PD-L1 was higher in dysplastic samples.
- IDO1 and PD-L1 expression in the lamina propria correlated with dysplasia grade and inflammation.
- Expression levels fluctuated during follow-up.
Conclusions:
- IDO1 and PD-L1 are modulated in oral dysplasia and linked to inflammation.
- Fluctuating expression limits their utility as biomarkers for oral dysplasia progression.
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