CD8+ and FoxP3+ T-cell infiltration in actinic cheilitis

Background: Differences in immune profile between actinic cheilitis (AC), a precursor of lip squamous cell carcinoma, and normal lip vermillion (NL) have not been elucidated. Objectives: To compare density, distribution, and ratios of CD8+ and FoxP3+ cells between AC and NL and assess their associations with clinicopathologic variables. Methods: Samples of AC and NL obtained between 2001 and 2013 at the College of Dentistry of the University of Concepcion, Chile, were retrospectively analyzed for immunohistochemical detection of CD8+ and FoxP3+ cells. Differences between groups were tested by Mann–Whitney U and Fisher's exact tests. Independent effects of cell densities and CD8/FoxP3 ratio with AC were assessed by multiple logistic regression analysis after adjustment for potential confounding. Results: A total of 62 AC and 24 NL biopsies were included. Densities of CD8+ and FoxP3+ cells in AC were significantly higher than in NL. Conversely, the CD8+/FoxP3+ ratio was significantly lower in AC as compared to NL. After adjustment for sun exposure, age, gender, and smoking status, a stromal FoxP3+ cell density higher than 0.35 cells/field was significantly associated with increased odds of AC (odds ratio [OR] = 5.01, 95% confidence interval [CI]: 1.18–21.31), while a stromal CD8+/FoxP3+ ratio higher than 5.91 was associated with decreased odds of AC (OR = 0.29, 95% CI: 0.08–1.08). Conclusions: AC is characterized by increased FoxP3+ cell infiltration and a reduced CD8/FoxP3 ratio as compared to NL. Therefore, increased infiltration of FoxP3+ cells relative to CD8+ cells may contribute to the transition from normal to preneoplastic stages in lip carcinogenesis.