Cancer-Associated Fibroblasts in Invasion Front Can be a Prognostic Predictor for Oral Squamous Cell Carcinoma

Tumor immune microenvironment (TME) is an important pathogenic component in cancer, and a therapeutic target. To examine the role of the TME, especially cancer-associated fibroblasts (CAFs) in oral squamous cell carcinoma (SCC), a retrospective cohort study of 684 patients with surgically resected tissues was performed. Clinicopathological variables and immuno-oncology markers were analyzed by immunohistochemistry (IHC) focusing on the invasion front of SCC, including α-smooth muscle actin-positive CAFs, CD163-positive M2-like tumor-associated macrophages (TAMs), CD68-positive pan-macrophages, tumor protein p53, and T-cell intracellular antigen 1 (TIA-1)-positive cytotoxic T-lymphocytes (CTLs) by IHC in invasion front of SCC were analyzed. Each of high infiltration of CAFs, high M2-like TAMs, high or negative p53 expression, and low TIA-1-positive CTLs was associated with poor survival of the patients. In a multivariate analysis, age ≥ 75 years, performance status ≥ 1, extranodal extension, vessel invasion, moderate and poorly differentiated histological grade, and high CAF infiltration were associated with poor 5-year overall survival (all HR > 1, p-values < 0.05). Among the immuno-oncology markers, IHC analysis of the CAFs was one of the most useful markers for predicting survival of patients with oral SCC. High infiltration of CAFs was associated with poor overall survival.