Immune evasion mechanisms and cutting-edge therapeutic strategies of PD-L1 pathway in oral squamous cell carcinoma: an umbrella review

Background: Oral squamous cell carcinoma (OSCC), a significant health burden in developing nations, is linked to risk factors such as tobacco use, alcohol consumption, betel nut chewing, HPV infection, and genetic susceptibility. A hallmark of OSCC is impaired T cell function, driven in part by the PD-L1/PD-1 immune checkpoint pathway, which enables tumor immune evasion and progression. Despite growing interest in immunotherapy, a focused synthesis of PD-L1 expression and its clinical implications in OSCC remains limited. This review aims to consolidate existing evidence on PD-L1 in OSCC, evaluating its expression patterns, correlation with disease progression, and therapeutic relevance. Methods: A systematic search was conducted across multiple databases to identify studies examining PD-L1 expression in OSCC and its relationship with clinicopathological parameters and immune response. Results: The findings revealed a higher PD-L1 positivity in female patients, non-smokers, and non-drinkers. Positive PD-L1 expression rate correlated with poor differentiation, lymph node metastasis, and advanced TNM stage. Although it didn’t significantly impact overall survival, higher PD-L1 expression was observed in HPV-positive patients and correlated with increased CD8+ TIL levels. Discussion: Understanding the role of PD-L1 in OSCC elucidates immune evasion mechanisms and offers insights into potential treatments, such as checkpoint inhibitors, for personalized therapies and innovative cancer treatments. This comprehensive synthesis provides valuable insights into the complex interplay between PD-L1 expression and OSCC progression, laying the groundwork for additional studies in this area.