University of Oulu

Sieviläinen, M., Passador-Santos, F., Almahmoudi, R., Christopher, S., Siponen, M., Toppila-Salmi, S., Salo, T., Al-Samadi, A. (2018) Immune checkpoints indoleamine 2,3-dioxygenase 1 and programmed death-ligand 1 in oral mucosal dysplasia. Journal of Oral Pathology and Medicine, 47 (8), 773-780. doi:10.1111/jop.12737

Immune checkpoints indoleamine 2,3‐dioxygenase 1 and programmed death‐ligand 1 in oral mucosal dysplasia

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Author: Sieviläinen, Meri1; Passador‐Santos, Fabricio2; Almahmoudi, Rabeia1;
Organizations: 1Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki
2Department of Pathology, São Leopoldo Mandic Research Centre
3Department of Mathematics and Statistics, University of Helsinki
4Department of Oral and Maxillofacial Diseases, Kuopio University Hospital
5Institute of Dentistry, University of Eastern Finland
6Department of Allergy, Helsinki University Hospital, University of Helsinki
7Medical Research Centre, Oulu University Hospital
8Department of Diagnostics and Oral Medicine, Research Group of Cancer Research and Translational Medicine, Medical Faculty, University of Oulu
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2018102938948
Language: English
Published: John Wiley & Sons, 2018
Publish Date: 2019-06-20
Description:

Abstract

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.

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Series: Journal of oral pathology & medicine
ISSN: 0904-2512
ISSN-E: 1600-0714
ISSN-L: 0904-2512
Volume: 47
Issue: 8
Pages: 773 - 780
DOI: 10.1111/jop.12737
OADOI: https://oadoi.org/10.1111/jop.12737
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
313 Dentistry
Subjects:
Funding: The authors acknowledge the funders of this study: the Sigrid Jusélius Foundation, cancer society of Finland, the Oulu University Hospital MRC grant, the Emil Aaltonen Foundation, the Helsinki University Central Hospital research funds, Eteläsuomalaisten ylioppilaiden säätiö, Helsingin seudun hammaslääkärit – Helsingforsregionens Tandläkare ry, and the Finnish Dental Society Apollonia.
Copyright information: This is the peer reviewed version of the following article: Sieviläinen, M., Passador-Santos, F., Almahmoudi, R., Christopher, S., Siponen, M., Toppila-Salmi, S., Salo, T., Al-Samadi, A. (2018) Immune checkpoints indoleamine 2,3-dioxygenase 1 and programmed death-ligand 1 in oral mucosal dysplasia. Journal of Oral Pathology and Medicine, 47 (8), 773-780. doi:10.1111/jop.12737, which has been published in final form at https://doi.org/10.1111/jop.12737. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.