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Vitamin D is an essential molecule for cellular homeostasis, playing a critical role in cell fate decisions including cell proliferation, differentiation, and viability. Accumulating evidence has revealed that expression of the vitamin D-metabolizing enzyme CYP24A1 is dysregulated in different types of human malignancy. CYP24A1 has been shown to be involved in the oncogenic property of a variety of carcinoma cells. However, the pathological relevance of CYP24A1 expression level in human oral malignancy remains to be clarified. In the present study, suppression of CYP24A1 expression in oral squamous cell carcinoma (OSCC) cells increased cell proliferation, invasive activity, colony formation efficacy, and tumor growth in vivo. In addition, knockout of CYP24A1 expression inhibited cell death induced by two different types of anticancer drugs, i.e., fluorouracil and cisplatin. Gene clustering by RNA-sequence analysis revealed that several signaling molecules associated with MYC are involved in CYP24A1-mediated oncogenic behaviors. Furthermore, decreased expression level of CYP24A1 was observed in 124/204 cases (61%) of OSCC and was shown to be associated with short relapse-free and overall survival periods. The results showed that a low expression level of CYP24A1 promotes the oncogenic activity of OSCC and is significantly associated with poor prognosis in patients with this malignancy. [ABSTRACT FROM AUTHOR]

Background: Tumor-infiltrating lymphocytes include tumor-reactive lymphocytes and regulatory T-cells. However, the prognostic value of tumor-infiltrating lymphocytes in oral squamous cell carcinoma (OSCC) remains unclear. Methods: We used immunohistochemistry to evaluate the presence of tumor-infiltrating FoxP3⁺ T-cells and CTLA-4⁺ cells in four distinct histological compartments (tumor parenchyma and stroma at the tumor center, and parenchyma and stroma at the invasive front) and assessed the association between the prevalence of these cells and the histopathological status of 137 patients with OSCC. Results: Five-year overall survival, disease-specific survival, and recurrence-free survival were favorable in patients with high numbers of FoxP3⁺ T-cells in the parenchyma of the invasive front. Recurrence-free survival and metastasis-free survival were decreased in patients with high numbers of CTLA-4⁺ cells in the parenchyma of the invasive front. Conclusions: The presence of FoxP3⁺ T-cells in the parenchyma of the invasive front may be a useful prognostic factor. Our results indicate that FoxP3⁺ T-cells may exert site-specific anti-tumor effects but may not play an immunosuppressive role in OSCC. In addition, our results suggest that CTLA-4+ cells suppress the function of FoxP3+ T-cells and promote anti‐tumor immunity in OSCC. [ABSTRACT FROM AUTHOR]

Background: The presence of tumor‐infiltrating lymphocytes (TILs) is associated with improved survival in head and neck squamous cell carcinoma. However, the prognostic value of TILs remains unclear in oral squamous cell carcinoma (OSCC). Methods: We evaluated the associations between tumor‐infiltrating CD8+ T‐cell density and survival in five distinct compartments in 139 OSCC cases. Results: There was a significant association between increased tumor‐infiltrating CD8+ T cells and their distribution. High parenchymal CD8+ T‐cell density at the invading tumor edge was associated with improved overall survival (OS) and disease‐specific survival (DSS; P < 0.01 and P < 0.01, respectively). High stromal CD8+ T‐cell density at the tumor periphery was also associated with improved recurrence‐free survival (RFS; P < 0.01). Cox regression analysis revealed that high stromal CD8+ T‐cell density at the tumor periphery and high parenchymal CD8+ T‐cell density at the invading edge were independent prognostic makers (hazard ratio: 0.38 and 0.19, 95% confidence interval, 0.18‐0.80 and 0.05‐0.72, P = 0.01 and 0.01, respectively) for RFS and OS, respectively. Conclusions: Assessment of CD8+ T cells at the parenchyma of the invading edge and peripheral stroma provides an indicator of tumor recurrence and prognosis. Assessment of CD8+ T cells at the parenchyma of the invading edge and peripheral stroma provides an indicator of tumor recurrence and prognosis. [ABSTRACT FROM AUTHOR]