Metabolic and Aging Influence on Anticancer Immunity in Oral Cancer.

This article focuses on the impact of aging and obesity on oral squamous cell carcinoma (OSCC) through their modulation of the tumor microenvironment (TME) and antitumor immunity. It highlights how both conditions contribute to an immunosuppressive TME, particularly via the recruitment and polarization of tumor-associated macrophages (TAMs) toward a protumoral M2-like phenotype, which supports tumor progression and immune evasion. The review also discusses the role of immune checkpoint molecules, such as PD-1 and PD-L1, in OSCC and the potential to enhance immunotherapy efficacy by therapeutically reprogramming TAMs to an antitumor M1-like state. Additionally, it addresses the influence of the oral microbiome, metabolic changes, and chronic inflammation associated with aging and obesity on OSCC development and progression, underscoring emerging therapeutic strategies targeting these pathways to improve patient outcomes.