Spatiotemporal remodeling of the tumor–immune interface during neoadjuvant immunotherapy for oral squamous cell carcinoma: pathological response, resistance, and dynamic biomarkers

Oral squamous cell carcinoma (OSCC) is locally aggressive and frequently associated with cervical lymph-node metastasis and postoperative recurrence. Recent clinical advances in perioperative immunotherapy have made the neoadjuvant setting an important window for investigating dynamic changes in the tumor–immune microenvironment under therapeutic pressure. However, pathological responses vary substantially among patients, and baseline biomarkers such as the PD-L1 combined positive score (CPS) and tumor mutational burden (TMB) do not reliably identify those most likely to benefit. Evidence from single-cell sequencing, spatial omics, multiplex imaging, and longitudinal liquid-biopsy studies indicates that pathological response is closely associated with antigen presentation, expansion-competent T cells, tertiary lymphoid structures, vascular routes of immune-cell entry, and myeloid–stromal remodeling. In contrast, impaired antigen presentation, T-cell exclusion, immunosuppressive macrophages, cancer-associated fibroblasts, hypoxic metabolism, and lymph-node-specific niches are associated with residual resistance. This review examines spatiotemporal changes at the tumor–immune interface before and after neoadjuvant immunotherapy for OSCC, with an emphasis on pathological response, mechanisms of resistance, and dynamic biomarkers. We also discuss the translational potential of these features for patient stratification and perioperative treatment decision-making.