Impact of Neoadjuvant Chemotherapy on PD-L1 Expression in Oral Squamous Cell Carcinoma: A Matched Biopsy-Resection Study.

Background: Programmed death ligand 1 (PD-L1) is essential for immune evasion and serves as a significant biomarker for immunotherapy in oral squamous cell carcinoma (OSCC). Nevertheless, the changes in its expression after neoadjuvant chemotherapy (NACT) are not well understood. This research sought to assess the variations in PD-L1 expression between matched pretreatment biopsy samples and post-NACT surgical specimens, while also correlating these results with clinicopathological characteristics.

Materials And Methods: The study comprised 130 patients with OSCC, of which 95 were treated with NACT while 35 acted as controls who did not receive NACT. PD-L1 expression was measured via immunohistochemistry (SP263 clone) on pretreatment biopsy samples and corresponding post-NACT resection specimens, employing Tumor Proportion Score (TPS), Immune Proportion Score (IPS), and Combined Positive Score (CPS) at several cut-off points (≥1%, ≥10%, ≥25%, and ≥50%). Statistical evaluations were performed using SPSS version 24.0.

Results: In post NACT, there was a significant variation in PD-L1 expression. A marked reduction in PD-L1 TPS was noted in T1 tumors, decreasing from 43.4% to 13.0% (p=0.039), as well as in tumors with a depth of invasion (DOI) less than 5mm, which dropped from 40.7% to 14.8%. Conversely, an increase in PD-L1 expression was observed in tumors at advanced nodal stages and those exhibiting lymphovascular invasion (LVI), perineural invasion (PNI), and tumor budding. The change in combined positive score (CPS) was significantly correlated with tumor budding (p=0.008), the worst pattern of invasion (WPOI) (p=0.036), DOI (p=0.030), and prognostic stage (p=0.026). In control cases, only minor alterations in PD-L1 status were detected between biopsy and resection specimens.

Conclusion: NACT did not lead to uniform or widespread changes in PD-L1 expression in OSCC. Significant alterations were limited to TPS in T1 tumors and CPS associations with certain pathological features, while most other comparisons showed no statistical significance. These findings suggest that PD-L1 expression after NACT should be interpreted cautiously, and larger studies are needed to clarify its clinical relevance.