Epithelial-Mesenchymal Transition, Immune Response, and Extracellular Matrix Remodelling in Oral Cancer

This retrospective study investigates the interplay between epithelial-mesenchymal transition (EMT) and immune response within the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC).

Immunohistochemistry was conducted on OSCC specimens to evaluate the expression of podoplanin (PDP), E-cadherin (CDH1), vimentin (VIM), fibronectin (FN), tenascin-C (TNC), and vascular endothelial growth factor (VEGF). Cancer-associated fibroblasts (CAFs) were identified by alpha-smooth muscle actin (α-SMA), and immune cells were quantified using CD66b for neutrophils and CD8 for T lymphocytes.

Higher α-SMA and moderate-to-strong VEGF expression were associated with reduced CDH1 and increased VIM and PDP expression (p < 0.05), indicating an EMT-like phenotype. Cases with elevated PDP-also linked to high α-SMA-showed increased CD66b⁺ cell density (p = 0.072). VEGF expression additionally correlated with greater tumor thickness and depth of invasion (p = 0.059). Strong TNC expression was associated with reduced CD8⁺ T-cell infiltration in the tumor centre and increased CD66b⁺ neutrophils (p < 0.046). Strong FN expression was linked to a higher neutrophil-to-lymphocyte ratio (p = 0.031). Elevated CD66b⁺ cell counts and a higher neutrophil-to-lymphocyte ratio were both significantly associated with poorer overall survival (p < 0.015).

These exploratory findings suggest that CAFs serve not only as a marker of stromal activation but may also contribute to immunomodulation and invasive tumor phenotype.