Involvement of the Programmed Death 1/Programmed Death Ligand 1 Pathway in the Immune Microenvironment of Chronic Periapical Lesions

Introduction and aims: This study aimed to determine the pathogenic role and clinicopathological significance of the immune microenvironment including the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway in chronic periapical lesions. Methods: A total of 20 chronic periapical lesi...

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Main Authors: Yujin Song, Seohee Park, Hyeseong Jin, Byungyoon Hyun, Kyu-Young Oh
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:International Dental Journal
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Online Access:http://www.sciencedirect.com/science/article/pii/S0020653925001637
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author Yujin Song
Seohee Park
Hyeseong Jin
Byungyoon Hyun
Kyu-Young Oh
author_facet Yujin Song
Seohee Park
Hyeseong Jin
Byungyoon Hyun
Kyu-Young Oh
author_sort Yujin Song
collection DOAJ
description Introduction and aims: This study aimed to determine the pathogenic role and clinicopathological significance of the immune microenvironment including the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway in chronic periapical lesions. Methods: A total of 20 chronic periapical lesions consisting of 10 periapical granulomas and 10 periapical cysts were included in this study. Immunohistochemistry was performed for immune cell populations, including PD-L1, PD-1, CD4, CD8, FOXP3, and CD20. Immune cell populations were quantitatively evaluated on digitized slides. The associations between each immune cell population and clinicopathological factors and between immune cell populations were statistically analysed. Results: Lesion size was positively associated with the density of PD-L1+ macrophages (P < .001, Fisher exact test; r = 0.455, P = .044, Pearson correlation analysis) and CD8+ cytotoxic T cells (P = .020, Fisher exact test; r = 0.471, P = .036, Pearson correlation analysis). No associations were found between immune cell populations and other clinicopathological factors, including age, sex, lesion location, and diagnosis. A moderate positive correlation was observed between the density of PD-L1+ macrophages and CD8+ cytotoxic T cells (r = 0.537, P = .015). The density of PD-1+ cells showed a strong positive correlation with the density of CD4+ helper T cells (r = 0.719, P < .001) and FOXP3+ regulatory T cells (r = 0.784, P < .001). Conclusion: These findings suggest that cytotoxic T cells are implicated in the progression of chronic periapical lesions, which may be regulated by PD-L1+ macrophages. PD-1 may be involved in helper T cell exhaustion and regulatory T cell activity in chronic periapical lesions. Clinical relevance: We demonstrated the involvement of PD-L1 and PD-1 in the regulation of T cell immunity in chronic periapical lesions. These findings suggest that activating the PD-1/PD-L1 pathway is a potential therapeutic strategy for chronic periapical lesions.
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spelling doaj-art-7ffa3beb7bfe4383ae12bd9d123229c12025-08-20T03:50:31ZengElsevierInternational Dental Journal0020-65392025-08-0175410087410.1016/j.identj.2025.100874Involvement of the Programmed Death 1/Programmed Death Ligand 1 Pathway in the Immune Microenvironment of Chronic Periapical LesionsYujin Song0Seohee Park1Hyeseong Jin2Byungyoon Hyun3Kyu-Young Oh4College of Dentistry, Dankook University, Cheonan, Republic of KoreaCollege of Dentistry, Dankook University, Cheonan, Republic of KoreaCollege of Dentistry, Dankook University, Cheonan, Republic of KoreaCollege of Dentistry, Dankook University, Cheonan, Republic of KoreaDepartment of Oral Pathology, College of Dentistry, Dankook University, Cheonan, Republic of Korea; Dankook University Dental Hospital, Cheonan, Republic of Korea; Corresponding author. Department of Oral Pathology, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea.Introduction and aims: This study aimed to determine the pathogenic role and clinicopathological significance of the immune microenvironment including the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway in chronic periapical lesions. Methods: A total of 20 chronic periapical lesions consisting of 10 periapical granulomas and 10 periapical cysts were included in this study. Immunohistochemistry was performed for immune cell populations, including PD-L1, PD-1, CD4, CD8, FOXP3, and CD20. Immune cell populations were quantitatively evaluated on digitized slides. The associations between each immune cell population and clinicopathological factors and between immune cell populations were statistically analysed. Results: Lesion size was positively associated with the density of PD-L1+ macrophages (P < .001, Fisher exact test; r = 0.455, P = .044, Pearson correlation analysis) and CD8+ cytotoxic T cells (P = .020, Fisher exact test; r = 0.471, P = .036, Pearson correlation analysis). No associations were found between immune cell populations and other clinicopathological factors, including age, sex, lesion location, and diagnosis. A moderate positive correlation was observed between the density of PD-L1+ macrophages and CD8+ cytotoxic T cells (r = 0.537, P = .015). The density of PD-1+ cells showed a strong positive correlation with the density of CD4+ helper T cells (r = 0.719, P < .001) and FOXP3+ regulatory T cells (r = 0.784, P < .001). Conclusion: These findings suggest that cytotoxic T cells are implicated in the progression of chronic periapical lesions, which may be regulated by PD-L1+ macrophages. PD-1 may be involved in helper T cell exhaustion and regulatory T cell activity in chronic periapical lesions. Clinical relevance: We demonstrated the involvement of PD-L1 and PD-1 in the regulation of T cell immunity in chronic periapical lesions. These findings suggest that activating the PD-1/PD-L1 pathway is a potential therapeutic strategy for chronic periapical lesions.http://www.sciencedirect.com/science/article/pii/S0020653925001637Immune microenvironmentPD-1PD-L1Periapical granulomaPeriapical cyst
spellingShingle Yujin Song
Seohee Park
Hyeseong Jin
Byungyoon Hyun
Kyu-Young Oh
Involvement of the Programmed Death 1/Programmed Death Ligand 1 Pathway in the Immune Microenvironment of Chronic Periapical Lesions
International Dental Journal
Immune microenvironment
PD-1
PD-L1
Periapical granuloma
Periapical cyst
title Involvement of the Programmed Death 1/Programmed Death Ligand 1 Pathway in the Immune Microenvironment of Chronic Periapical Lesions
title_full Involvement of the Programmed Death 1/Programmed Death Ligand 1 Pathway in the Immune Microenvironment of Chronic Periapical Lesions
title_fullStr Involvement of the Programmed Death 1/Programmed Death Ligand 1 Pathway in the Immune Microenvironment of Chronic Periapical Lesions
title_full_unstemmed Involvement of the Programmed Death 1/Programmed Death Ligand 1 Pathway in the Immune Microenvironment of Chronic Periapical Lesions
title_short Involvement of the Programmed Death 1/Programmed Death Ligand 1 Pathway in the Immune Microenvironment of Chronic Periapical Lesions
title_sort involvement of the programmed death 1 programmed death ligand 1 pathway in the immune microenvironment of chronic periapical lesions
topic Immune microenvironment
PD-1
PD-L1
Periapical granuloma
Periapical cyst
url http://www.sciencedirect.com/science/article/pii/S0020653925001637
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