Number of FoxP3+ regulatory T-cells are associated with recurrence in vulvar squamous cell carcinoma

Abstract

Objective: Surgical management is essential in early-stage vulvar squamous cell carcinoma (SCC), but these surgical procedures often cause significant morbidity. Immunotherapy may be a new treatment option in these patients. FoxP3+ Tregs suppress anti-tumor immune responses. High intratumoral FoxP3+ Treg infiltration has been reported to be associated with poor prognosis in most solid tumors. However, there are also conflicting results. We evaluated FoxP3+ lymphocyte infiltration in vulvar SCC and aimed to determine its relationship with prognosis and clinicopathological parameters.

Methods: Cases diagnosed with vulvar SCC in our department were retrospectively reviewed. The paraffin block that best reflects the morphology was selected, and immunohistochemical studies were performed in accordance with the manufacturer's instructions. FoxP3+ lymphocyte counts were made in tumoral stroma and within tumoral cell islands separately in hot-spot areas.

Results: We found a positive correlation between high FoxP3+ lymphocyte count and good prognostic parameters. There was less recurrence in the group with high FoxP3+ lymphocyte counts in tumoral cell islands. Overall survival was not statistically different between these groups. Less lymphovascular invasion was observed in the group with high lymphocyte count in the tumoral stroma.

Conclusion: In vulvar SCC, FoxP3+ Treg infiltration into the tumor stroma and into tumoral cell islands is associated with good prognostic features. In these tumors, stage appeared as the only independent prognostic parameter. Studies to be conducted in larger series may reveal whether Tregs can be targeted in cancer treatment.

Keywords: FoxP3; Prognosis; Squamous Cell Carcinoma; Treg; Vulva.

Fig. 1. Receiver operating characteristic curve for FoxP3 positive lymphocyte in the tumoral stromal area (A), and FoxP3 positive lymphocyte in the intraepithelial area (B).

Fig. 2. Tumors with high (A) and low (B) FoxP3+ lymphocyte counts in the stromal area high (C) and low (D) FoxP3+ lymphocyte counts in intratumoral areas of vulvar squamous cell carcinomas (×400).

Fig. 3. Graphs showing the effects of FoxP3+ lymphocyte count in intratumoral and stromal areas on overall survival and disease-free survival. There is only a significant correlation between the number of lymphocytes in the intratumoral area and disease-free survival.