SPATIAL ORGANIZATION OF THE TUMOR IMMUNE MICROENVIRONMENT IN ORAL SQUAMOUS CELL CARCINOMA: IMPLICATIONS FOR DIAGNOSIS, PROGNOSIS AND IMMUNOTHERAPY

Abstract

Background: Oral squamous cell carcinoma (OSCC) develops inbetween a complex tumor immune microenvironment (TIME) which consists of lymphocytes, fibroblast, malignant cells, myeloid cells, endothelial cells & extracellular matrix. Increasing evidence suggest that the biological importance of these components depends not only on their abundance but also on their spatial distribution & interactions. Objective: This narrative review summarizes the current evidence about the spatial organization of the TIME in OSCC & discusses its implications for prognosis, diagnosis & immunotherapy. Methods: PubMed-indexed literature addressing the OSCC/HNSCC immune microenvironment, tumor-infiltrating lymphocytes, tertiary lymphoid structures (TLS), immune checkpoints therapy and spatial transcriptomics was narratively reviewed. Results: Spatially distinct populations of CD8+ T cells, regulatory T cells, B cells, macrophages, myeloid-derived suppressor cells & cancer-associated fibroblasts contribute to immune activation or suppression. TLS, particularly their maturity and proximity to tumor cells, have emerged as important spatial determinants of prognosis and treatment response. Spatial transcriptomics and multiplex imaging have revealed metabolic, myeloid and stromal niches that are not apparent using conventional histopathology. Conclusion: Spatial profiling may complement conventional clinicopathological & molecular biomarkers. Integration of immune-cell localization, , stromal organization, molecular signatures TLS architecture could improve risk stratification as well as facilitate more precise immunotherapy in OSCC.