Distinct expression patterns of Toll-like receptor 7 in tumour cells and fibroblast-like cells in oral squamous cell carcinoma.

Aims Toll-like receptor ( TLR)-7 agonists have been used in cancer immunotherapy, but tumour heterogeneity means that TLR-7 activity is variable in different components of the tumour microenvironment and the characteristics of TLR-7 in oral squamous cell carcinoma ( OSCC) are unclear. Methods and results Twenty healthy oral tissues, 50 oral leukoplakia tissues and 166 retrospective primary OSCC samples were collected for immunohistochemical staining of TLR-7 and showed up-regulated expression during carcinogenesis. Moreover, patients with high expression of TLR-7 in tumour cells ( TCs) had poor differentiation and prognosis. Interestingly, patients with high expression of TLR-7 in stroma fibroblast-like cells ( FLCs) had low tumour stage, no lymph node metastasis ( LNM) and better prognosis. Furthermore, Ki-67, CD3, CD4, CD8 and forkhead box protein 3 (FoxP3)+ tumour-infiltrated lymphocytes were assessed and we found that TLR-7high TCs were infiltrated by fewer CD3+ CD4+ but more FoxP3+ lymphocytes. Importantly, patients with TLR-7low TCs and TLR-7high FLCs had less FoxP3+ lymphocyte infiltration and longer survival time than those with TLR-7high TCs/ TLR-7low FLCs, although TLR-7 was not an independent prognostic factor for OSCC. Conclusions The low expression of TLR-7 in tumour and high expression of TLR-7 in stroma predict a good clinical outcome for OSCC patients, and stroma FLCs might be amenable to immunotherapy by a TLR-7 agonist. [ABSTRACT FROM AUTHOR]