Forkhead box-P3⁺ regulatory T cells and toll-like receptor 2 co-expression in oral squamous cell carcinoma

The function of forkhead box-P3 (FoxP3) regulatory T cells (Treg) and toll-like receptor (TLR)2 protein in the oral cancer microenvironment is not fully understood, but evidence from other malignancies suggests it is likely they are involved with tumour development and progression. The aim of this study was to investigate the distribution of FoxP3⁺cells, TLR2⁺ cells and double-labelled FoxP3⁺TLR2⁺ immune cells in oral squamous cell carcinoma (OSCC), using immunohistochemistry (IHC) and immunofluorescence (IF).

25 archival cases of OSCC were immunostained with anti-FoxP3 and anti-TLR2 antibodies. Inflamed hyperplastic oral mucosal tissues were used as controls. The proportion of single-labelled, double-labelled and negative cells was determined.

A higher frequency of double-labelled FoxP3⁺TLR2⁺ Tregs was observed within the immune cells of OSCC compared to inflamed controls using IHC (p<0.05). Cell-to-cell contact between single-stained TLR2⁺ cells and FoxP3⁺ cells was noted. Double IF studies validated demonstration of co-expression of FoxP3⁺/TLR2⁺ immune cells in OSCC.

The presence of FoxP3⁺TLR2⁺ cells within the OSCC microenvironment may represent a dendritic cell-dependent pathway capable of inhibiting Treg suppressive activity, potentially enhancing the anti-tumour response. Modulation of TLR2-Treg interactions should be further explored to determine if they have a role in the therapeutic management of OSCC.