PD1 expression and correlation with its ligands in oral cancer specimens and peripheral blood |
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| Authors: | Falk Wehrhan Manuel Weber Christoph Baran Abbas Agaimy Maike Büttner-Herold Marco Kesting Jutta Ries |
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| Institution: | 1. Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Germany;2. Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Germany;3. Institute of Pathology, Department of Nephropathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Germany;1. Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan;2. Department of Cranio-Maxillofacial Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland;3. Division of Nutrition, Saitama Medical Center, Saitama Medical University, Saitama, Japan;4. Community Health Science Center, Saitama Medical University, Saitama, Japan;5. Department of Hepato-Biliary-Pancreatic and Pediatric Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan;1. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China;2. Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China;3. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Ibb University, Ibb, Yemen;4. Head of the Department of Orthognathic and TMJ Surgery, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China;1. Beijing Tongren Hospital, Capital Medical University, Beijing, China;2. Harbin Medical University, Heilongjiang, China;3. Beijing Tongren Eye Center, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing, China;1. Department of Oral and Maxillofacial Surgery, Christian Albrechts University, Kiel, Germany;2. Department of Periodontology, Faculty of Dentistry, Çank?r? Karatekin University, Çank?r?, Turkey |
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| Abstract: | ObjectivesThis study analyzed the expression of the PD1 receptor in tumor tissue and peripheral blood of oral squamous cell carcinoma (OSCC) patients, and correlated it with the PD1 ligands PD-L1 and PD-L2. The currently low response rates of checkpoint inhibitor treatment in OSCC could be increased by a better understanding of immune checkpoint biology. Despite evidence in the literature for upregulation of PD1 checkpoint ligands in OSCC tissue, there has been no correlation analysis of the PD1 receptor with its ligands in tissue specimens and peripheral blood of OSCC patients.Materials and methodsAn RT-qPCR analysis of PD1 mRNA expression was performed in oral cancer specimens, healthy mucosa, and corresponding blood samples. A cut-off point (COP) was determined and a chi-square (χ2) test was carried out. PD1 expression was correlated with previously reported PD-L1 and PD-L2 expression values using the Spearman test.ResultsTissue and blood specimens of 48 OSCC patients and 26 healthy individuals were analyzed. PD1 expression in OSCC specimens was significantly increased (p = 0.006) compared with healthy oral mucosa. PD1 overexpression in tissue samples showed a significant association with the presence of malignancy (p = 0.006). PD1 expression in tissue samples showed a significant positive correlation (p < 0.001) with the ligands PD-L1 and PD-L2. In contrast, there was no correlation between PD1 and its ligands in blood samples. However, there was a significant positive correlation (p < 0.001) between the ligands PD-L1 and PD-L2, both in tissue and blood samples.ConclusionsIncreased PD1 expression might be a manifestation of T-cell exhaustion in OSCC specimens, leading to immune tolerance. PD-L1/PD-L2-PD1 interaction may be a major mediator of local immunosuppression in OSCC, requiring advanced multimodal treatment protocols. |
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| Keywords: | PD1 PD-L1 PD-L2 Immune checkpoint RT-qPCR OSCC |
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