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 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.