Song Yujin, Park Seohee, Jin Hyeseong, Hyun Byungyoon, Oh Kyu-Young
College of Dentistry, Dankook University, Cheonan, Republic of Korea.
Department of Oral Pathology, College of Dentistry, Dankook University, Cheonan, Republic of Korea; Dankook University Dental Hospital, Cheonan, Republic of Korea.
Int Dent J. 2025 Aug;75(4):100874. doi: 10.1016/j.identj.2025.100874. Epub 2025 Jun 25.
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.
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.
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).
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.
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.
本研究旨在确定免疫微环境（包括程序性死亡1（PD-1）/程序性死亡配体1（PD-L1）通路）在慢性根尖周病变中的致病作用及临床病理意义。
本研究共纳入20例慢性根尖周病变，其中包括10例根尖周肉芽肿和10例根尖周囊肿。对免疫细胞群体进行免疫组织化学检测，包括PD-L1、PD-1、CD4、CD8、FOXP3和CD20。在数字化切片上对免疫细胞群体进行定量评估。对各免疫细胞群体与临床病理因素之间以及免疫细胞群体之间的相关性进行统计学分析。
病变大小与PD-L1+巨噬细胞密度呈正相关（P <.001，Fisher精确检验；r = 0.455，P =.044，Pearson相关分析）以及与CD8+细胞毒性T细胞密度呈正相关（P =.020，Fisher精确检验；r = 0.471，P =.036，Pearson相关分析）。未发现免疫细胞群体与其他临床病理因素之间存在关联，包括年龄、性别、病变位置和诊断。观察到PD-L1+巨噬细胞密度与CD8+细胞毒性T细胞密度之间存在中度正相关（r = 0.537，P =.015）。PD-1+细胞密度与CD4+辅助性T细胞密度呈强正相关（r = 0.719，P <.001）以及与FOXP3+调节性T细胞密度呈强正相关（r = 0.784，P <.001）。
这些发现表明细胞毒性T细胞与慢性根尖周病变的进展有关，这可能受PD-L1+巨噬细胞调节。PD-1可能参与慢性根尖周病变中辅助性T细胞耗竭和调节性T细胞活性。
我们证明了PD-L1和PD-1参与慢性根尖周病变中T细胞免疫的调节。这些发现表明激活PD-1/PD-L1通路是慢性根尖周病变的一种潜在治疗策略。
