Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia
Background: The programmed cell death ligand 1/programmed cell death receptor 1 (PD-L1/PD-1) Immune Checkpoint is an important modulator of the immune response. Overexpression of the receptor and its ligands is involved in immunosuppression and the failure of an immune response against tumor cells....
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MDPI AG
2021-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/2/194 |
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| author | Jutta Ries Abbas Agaimy Falk Wehrhan Christoph Baran Stella Bolze Eva Danzer Silke Frey Jonathan Jantsch Tobias Möst Maike Büttner-Herold Claudia Wickenhauser Marco Kesting Manuel Weber |
| author_facet | Jutta Ries Abbas Agaimy Falk Wehrhan Christoph Baran Stella Bolze Eva Danzer Silke Frey Jonathan Jantsch Tobias Möst Maike Büttner-Herold Claudia Wickenhauser Marco Kesting Manuel Weber |
| author_sort | Jutta Ries |
| collection | DOAJ |
| description | Background: The programmed cell death ligand 1/programmed cell death receptor 1 (PD-L1/PD-1) Immune Checkpoint is an important modulator of the immune response. Overexpression of the receptor and its ligands is involved in immunosuppression and the failure of an immune response against tumor cells. PD-1/PD-L1 overexpression in oral squamous cell carcinoma (OSCC) compared to healthy oral mucosa (NOM) has already been demonstrated. However, little is known about its expression in oral precancerous lesions like oral leukoplakia (OLP). The aim of the study was to investigate whether an increased expression of PD-1/PD-L1 already exists in OLP and whether it is associated with malignant transformation. Material and Methods: PD-1 and PD-L1 expression was immunohistologically analyzed separately in the epithelium (E) and the subepithelium (S) of OLP that had undergone malignant transformation within 5 years (T-OLP), in OLP without malignant transformation (N-OLP), in corresponding OSCC and in NOM. Additionally, RT-qPCR analysis for PD-L1 expression was done in the entire tissues. Additionally, the association between overexpression and malignant transformation, dysplasia and inflammation were examined. Results: Compared to N-OLP, there were increased levels of PD-1 protein in the epithelial and subepithelial layers of T-OLP (p<sub>E</sub> = 0.001; p<sub>S</sub> = 0.005). There was no significant difference in PD-L1 mRNA expression between T-OLP and N-OLP (<i>p</i> = 0.128), but the fold-change increase between these groups was significant (Relative Quantification (RQ) = 3.1). In contrast to N-OLP, the PD-L1 protein levels were significantly increased in the epithelial layers of T-OLP (<i>p</i> = 0.007), but not in its subepithelial layers (<i>p</i> = 0.25). Importantly, increased PD-L1 levels were significantly associated to malignant transformation within 5 years. Conclusion: Increased levels of PD-1 and PD-L1 are related to malignant transformation in OLP and may represent a promising prognostic indicator to determine the risk of malignant progression of OLP. Increased PD-L1 levels might establish an immunosuppressive microenvironment, which could favor immune escape and thereby contribute to malignant transformation. Hence, checkpoint inhibitors could counteract tumor development in OLP and may serve as efficient therapeutic strategy in patients with high-risk precancerous lesions. |
| first_indexed | 2024-03-09T00:50:30Z |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T00:50:30Z |
| publishDate | 2021-02-01 |
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| series | Biomedicines |
| spelling | doaj.art-5ea5a0a50b9e43beb2c5d2b67279fa3c2023-12-11T17:13:59ZengMDPI AGBiomedicines2227-90592021-02-019219410.3390/biomedicines9020194Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral LeukoplakiaJutta Ries0Abbas Agaimy1Falk Wehrhan2Christoph Baran3Stella Bolze4Eva Danzer5Silke Frey6Jonathan Jantsch7Tobias Möst8Maike Büttner-Herold9Claudia Wickenhauser10Marco Kesting11Manuel Weber12Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, 91054 Erlangen, GermanyInstitute of Clinical Microbiology and Hygiene, University Hospital of Regensburg and University of Regensburg, 93053 Regensburg, GermanyDepartment of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Nephropathology, Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyInstitute of Pathology, Halle (Saale) University Hospital, Martin-Luther University Halle-Wittenberg (MLU), 06108 Halle (Saale), GermanyDepartment of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyBackground: The programmed cell death ligand 1/programmed cell death receptor 1 (PD-L1/PD-1) Immune Checkpoint is an important modulator of the immune response. Overexpression of the receptor and its ligands is involved in immunosuppression and the failure of an immune response against tumor cells. PD-1/PD-L1 overexpression in oral squamous cell carcinoma (OSCC) compared to healthy oral mucosa (NOM) has already been demonstrated. However, little is known about its expression in oral precancerous lesions like oral leukoplakia (OLP). The aim of the study was to investigate whether an increased expression of PD-1/PD-L1 already exists in OLP and whether it is associated with malignant transformation. Material and Methods: PD-1 and PD-L1 expression was immunohistologically analyzed separately in the epithelium (E) and the subepithelium (S) of OLP that had undergone malignant transformation within 5 years (T-OLP), in OLP without malignant transformation (N-OLP), in corresponding OSCC and in NOM. Additionally, RT-qPCR analysis for PD-L1 expression was done in the entire tissues. Additionally, the association between overexpression and malignant transformation, dysplasia and inflammation were examined. Results: Compared to N-OLP, there were increased levels of PD-1 protein in the epithelial and subepithelial layers of T-OLP (p<sub>E</sub> = 0.001; p<sub>S</sub> = 0.005). There was no significant difference in PD-L1 mRNA expression between T-OLP and N-OLP (<i>p</i> = 0.128), but the fold-change increase between these groups was significant (Relative Quantification (RQ) = 3.1). In contrast to N-OLP, the PD-L1 protein levels were significantly increased in the epithelial layers of T-OLP (<i>p</i> = 0.007), but not in its subepithelial layers (<i>p</i> = 0.25). Importantly, increased PD-L1 levels were significantly associated to malignant transformation within 5 years. Conclusion: Increased levels of PD-1 and PD-L1 are related to malignant transformation in OLP and may represent a promising prognostic indicator to determine the risk of malignant progression of OLP. Increased PD-L1 levels might establish an immunosuppressive microenvironment, which could favor immune escape and thereby contribute to malignant transformation. Hence, checkpoint inhibitors could counteract tumor development in OLP and may serve as efficient therapeutic strategy in patients with high-risk precancerous lesions.https://www.mdpi.com/2227-9059/9/2/194immune checkpointsPD-1PD-L1oral leukoplakiaOSCCmalignant transformation |
| spellingShingle | Jutta Ries Abbas Agaimy Falk Wehrhan Christoph Baran Stella Bolze Eva Danzer Silke Frey Jonathan Jantsch Tobias Möst Maike Büttner-Herold Claudia Wickenhauser Marco Kesting Manuel Weber Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia Biomedicines immune checkpoints PD-1 PD-L1 oral leukoplakia OSCC malignant transformation |
| title | Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia |
| title_full | Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia |
| title_fullStr | Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia |
| title_full_unstemmed | Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia |
| title_short | Importance of the PD-1/PD-L1 Axis for Malignant Transformation and Risk Assessment of Oral Leukoplakia |
| title_sort | importance of the pd 1 pd l1 axis for malignant transformation and risk assessment of oral leukoplakia |
| topic | immune checkpoints PD-1 PD-L1 oral leukoplakia OSCC malignant transformation |
| url | https://www.mdpi.com/2227-9059/9/2/194 |
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