Senescent Periodontal Ligament Stem Cells as Drivers of Myeloid-Derived Suppressor Cell Recruitment in Periodontitis-Associated Oral Squamous Cell Carcinoma

Abstract

OSCC remains one of the most common oral malignancies and continues to be associated with high morbidity and mortality. Several studies suggests that chronic periodontitis contributes to oral carcinogenesis by creating an inflammatory and immunosuppressive microenvironment. Continuous microbial stimulation, oxidative stress, and inflammatory mediator release promotes tissue destruction and favour tumour initiation and progression.
PDLSCs play a central role in maintaining periodontal homeostasis and regeneration; however, a prolonged inflammatory environment induces cellular senescence, resulting in the development of SASP. Senescent PDLSCs secrete inflammatory cytokines, chemokines, growth factors, and MMPs that can alter the local immune microenvironment. Among the immune cells involved in chronic inflammation, MDSCs are key mediators of immune suppression and tumour progression. MDSCs inhibit CD8⁺ T-cell and NK-cell activity, promote Treg expansion, and facilitate angiogenesis, EMT, tumour invasion, thereby establishing a tumour supportive microenvironment.