Tumor microenvironment in oral squamous cell carcinoma: Implications for novel therapies

Oral squamous cell carcinoma (OSCC) has a complex tumor microenvironment (TME) that modulates tumor growth, metastasis, and treatment response. This review intends to shed light on the key components of the TME, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), immunological cells, endothelial cells, and the extracellular matrix (ECM), as well as their functions in OSCC biology. We address how interactions within the TME lead to tumor growth, treatment resistance, and immune evasion, focusing on current clinical studies that target these processes. In addition, we evaluate emerging therapeutic methods, such as immune checkpoint inhibitors, CAR-T cell therapy, anti-angiogenic medicines, and ECM remodeling inhibitors, which have shown promise in clinical trials. Despite the obstacles faced by TME heterogeneity and the requirement for robust biomarkers, personalized medicine approaches based on TME profiling hold great promise for improving treatment results. This review underlines the necessity of ongoing research to integrate TME-focused medicines into clinical practice and provides future options for overcoming resistance and improving therapeutic efficacy by targeting both tumor cells and their microenvironment.