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Cancer-Associated Fibroblasts in Invasion Front Can be a Prognostic Predictor for Oral Squamous Cell Carcinoma
Yuuki Ishii1,2, Joaquim Carreras1, Yukie Yara Kikuchi1
1Department of Pathology, School of Medicine, Tokai University, Tokyo, Japan.
Pathology International
|June 1, 2026
Summary
High infiltration of cancer-associated fibroblasts (CAFs) is linked to poor survival in oral squamous cell carcinoma (SCC) patients. This finding highlights CAFs as a key prognostic marker in oral cancer.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- The tumor immune microenvironment (TME) plays a critical role in cancer progression and represents a therapeutic target.
- Cancer-associated fibroblasts (CAFs) are key components of the TME, influencing oral squamous cell carcinoma (SCC) development.
Purpose of the Study:
- To investigate the prognostic significance of CAFs and other immuno-oncology markers in oral SCC.
- To analyze the association between CAF infiltration and patient survival outcomes.
Main Methods:
- Retrospective cohort study of 684 oral SCC patients with surgically resected tissues.
- Immunohistochemistry (IHC) analysis of CAFs (α-smooth muscle actin), M2-like TAMs (CD163), pan-macrophages (CD68), p53, and cytotoxic T-lymphocytes (CTLs, TIA-1) at the invasion front.
- Multivariate analysis of clinicopathological variables and immuno-oncology markers for survival prediction.
Main Results:
- High infiltration of CAFs, M2-like TAMs, high/negative p53 expression, and low CTLs were associated with poor patient survival.
- Multivariate analysis identified age, performance status, extranodal extension, vessel invasion, histological grade, and high CAF infiltration as predictors of poor 5-year overall survival.
- CAF infiltration emerged as a highly useful marker for predicting survival in oral SCC.
Conclusions:
- High CAF infiltration is a significant independent predictor of poor overall survival in oral SCC.
- Targeting CAFs within the TME may offer a potential therapeutic strategy for oral SCC.
- Immunohistochemical analysis of CAFs provides valuable prognostic information for oral SCC patients.
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