The role of programmed death receptor (PD-)1/PD-ligand (L)1 in periodontitis and cancer

Sep 21, 2026

The programmed-death-ligand-1 (PD-L1) is an immune-modulating molecule constitutively expressed on multiple immune cells, epithelial cells, and many cancer cells. As a costimulatory ligand, PD-L1 can weaken T-cell–mediated immunity by engaging PD-1 on activated T-cells, triggering apoptosis or anergy through related signaling pathways. PD-L1 upregulation in cancers, including oral squamous cell carcinoma, supports tumor immune escape and poor prognosis, with links to periodontitis and EMT. Exosomal PD-L1 may promote immunosuppression, while PD-1/PD-L1 checkpoint inhibitors show prognostic impact and therapeutic resistance may develop, motivating further mechanistic research.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

Keywords

Introduction

Periodontitis and microbial biofilm

PD-1/PD-L1 biology and signaling

DOI: 10. 1111/prd.12548 R E V I E W A RT I C L E The role of programmed death receptor (PD-)1/PD-ligand (L)1 in periodontitis and cancer Sabine Groeger1,2 | Joerg Meyle1 1Department of Periodontology, Dental School, Justus-Liebig-University of Giessen, Giessen, Germany 2Department of Orthodontics, Dental School, Justus-Liebig-University of Giessen, Giessen, Germany Correspondence Sabine Groeger, Departments of Periodontology and Orthodontics, Dental School, Justus-Liebig-University of Giessen, Schlangenzahl 14, Giessen 35392, Germany. Email: [sabine.e.groeger@dentist. med](sabine.e.groeger@dentist. med). [uni-giessen.de](uni-giessen.de) Abstract The programmed-death-ligand-1 (PD-L1) is an immune-modulating molecule that is constitutively expressed on various immune cells, different epithelial cells and a multitude of cancer cells. It is a costimulatory molecule that may impair T-cell mediated immune response. Ligation to the programmed-death-receptor (PD)-1, on activated T-cells and further triggering of the related signaling pathways can induce T-cells apoptosis or anergy. The upregulation of PD-L1 in various cancer types, including oral squamous cell carcinomas, was demonstrated and has been linked to immune escape of tumors and poor prognosis. A bidirectional relationship exists between the increased PD-L1 expression and periodontitis as well as the epithelial–mesenchymal transition (EMT), a process of interconversion of epithelial cells to mesenchymal cells that may induce immune escape of tumors. Interaction between exosomal PD-L1 and PD-1 on T-cells may cause immunosuppression by blocking the activation and proliferation of T-cells. The efficacy and importance of treatment with PD-1/PD-L1 checkpoint inhibitors and their prognostic influence on human cancers was demonstrated. Regarding PD-1/PD-L1 checkpoint inhibitors, resistances exist or may develop, basingon various factors. Further investigations of the underlying mechanisms will help to overcome the therapeutic limitations that result from resistances and to develop new strategies for the treatment of cancer. K E Y WO R D S cancer, EMT, exosomes, immune checkpoint, immune escape, PD-L1, periodontitis 1 | INTRODUCTION Periodontitis is characterized by a chronic inflammation that is initialized by a microbial biofilm that over the time leads to the destruction of periodontium. Tooth-attached microbial biofilm that adhere to the teeth = tooth plaques are prerequisite but not the only cause of periodontitis. The bacterial challenge induces an inflammatory host response that induces the destructive processes of the periodontium.1 Over 700 bacterial species were detected in the oral biofilm.2 From this number 300 were demonstrated to administer to the periodontal pockets biofilm. The number of bacterial species that are closely associated to initiation and progression of periodontal diseases was found to be considerably smaller.3 This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2024 The Authors. Periodontology 2000 published by John Wiley & Sons Ltd. Porphyromonas gingivalis (P. gingivalis), a gram-negative coccoid anaerobic and asaccharolytic rod, is prevalently detected in the oral cavity and regarded as one of the keystone pathogens of periodontitis.4 The programmed death ligand 1 (PD-L1) is known as immunemodulating molecule that is constitutively expressed on cells of the myeloid cell lineage, including macrophages and dendritic cells (DCs) .5–7 In epithelial and endothelial lineages of the lymphoid system, it is expressed after activation by interferon (INF)-γ and tumor necrosis factor (TNF)-α .8 PD-L1 is a ligand for the programmed death receptor (PD)-1, that is described as inhibitory receptor expressed on activated CD8

FAQs

What is PD-L1 and how does it affect immune responses?

PD-L1 is an immune-modulating molecule expressed on various immune and cancer cells. By engaging PD-1 on activated T-cells, it can induce T-cell apoptosis or anergy and impair T-cell mediated immunity.

How are periodontitis and increased PD-L1 expression connected?

The document describes a bidirectional relationship between increased PD-L1 expression and periodontitis. It links this association to epithelial–mesenchymal transition (EMT), which may contribute to tumor immune escape.

What role do PD-1/PD-L1 checkpoint inhibitors play, and why are resistances a concern?

Treatment with PD-1/PD-L1 checkpoint inhibitors is described as having efficacy and prognostic influence in human cancers. The text also notes that resistances exist or may develop, and further studies are needed to address therapeutic limitations.

Sep 21, 2026

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