Metformin as an immunomodulatory agent in enhancing head and neck squamous cell carcinoma therapies

Head and neck squamous cell carcinoma (HNSCC) remains a significant clinical challenge due to its aggressive behavior and poor prognosis, making the development of novel therapeutics with enhanced efficacy and minimal side effects critical. Metformin, a widely used antidiabetic agent, has recently emerged as a potential adjunctive therapy for HNSCC, exhibiting both direct anti-tumor and immunomodulatory effects. This review comprehensively explores the multifaceted role of metformin in shaping the tumor immune microenvironment within HNSCC. We emphasize its pivotal role in modulating immune cell populations and its potential for synergistic action with immunotherapeutic strategies. Furthermore, we address the current challenges associated with optimizing dosing regimens, identifying predictive biomarkers, and integrating metformin with immunotherapy. By dissecting these aspects, this review aims to pave the way for the development of personalized HNSCC treatment strategies that fully exploit the therapeutic potential of metformin.