Periodontitis-Induced Immune Reprogramming: Implications for Cancer Immunotherapy Response

Background: Chronic periodontitis is a prevalent inflammatory disease. It goes beyond the oral cavity, exerting systemic immunomodulatory effects through continuous low-grade inflammation, microbial dysbiosis, and cytokine spillover. Accumulating evidence suggests that the immunological consequences of periodontitis may influence systemic immune homeostasis and alter responses to cancer immunotherapies, specifically checkpoint blockade. Objectives: This narrative review describes how periodontal inflammation induces systemic immune reprogramming. It also investigates possible effects on the efficacy of immunotherapy. Methods: The paper synthesizes current findings on molecular and cellular mechanisms linking periodontitis to immune dysfunction. It underscores the mutual signaling pathways NF-κB, STAT3, and PD-1/PD-L1 that connect oral and systemic immunity. Results: Chronic periodontal inflammation reprograms innate and adaptive immune responses. It elevates proinflammatory mediators, such as IL-1β, IL-6, and TNF-α. It alters T-cell polarization and promotes myeloid cell "training". This process may lead to immune exhaustion, impaired antigen presentation, and treatment resistance. Preclinical and new clinical data suggest that controlling periodontal inflammation may partially reduce systemic inflammatory burden, although clinical evidence in immunotherapy-treated cancer cohorts remains limited. Conclusions: Periodontal health should be considered in the management of immunotherapy. This can facilitate new studies that integrate oral and systemic immunology. Understanding the two-way link between periodontal inflammation and systemic immune reprogramming may offer fresh opportunities for personalized immunomodulation and combined interventions.