Assessment of expression of toll-like receptors 2, 3 and 4 in laryngeal carcinoma

Abstract

Head and neck cancers remain a big challenge for oncology. Among them laryngeal carcinomas predominate. In spite of abundant inflammatory cell infiltrates containing several immunologically competent cells, patients with head and neck cancers show markedly suppressed anti-tumor response. In general, cancer cells use strategies to avoid recognition and destruction by the immune system. Toll-like receptors 1-13 (TLRs) are crucial for activation of innate immunity and secondarily for the induction of acquired response. TLRs are mainly expressed on cells of the immune system, but they have been demonstrated on endothelial and epithelial cells. Ligand binding to TLR leads to the activation of several genes, predominantly proinflammatory ones such as IL-1 and TNF-alpha and maturation of professional antigen presenting cells (APC) i.e., dendritic cells. It can cause better tumor antigen presentation by APC. The aim of this study was the evaluation of expression of TLR-2, TLR-3 and TLR-4 in the microenvironment of laryngeal carcinoma. Tumor specimens (n = 20, male patients aged 43-77 years, mean 57 years) from patients subjected to total laryngectomy. Immunohistochemistry and indirect immunoflourescence on frozen tissue sections. Cancer tissue: portion of cancer cells manifested membrane and/or cytoplasmic expression of TLR-2, TLR-3 and TLR-4. The most frequent expression on tumor cells was TLR-2 and the least expression of TLR-4. Inflammatory infiltrates: in all cases inflammatory cell infiltrates of various intensities were present, both in tumor mass and tumor stroma. Expression of all TLRs tested, both, membrane and cytoplasmic ones were shown on inflammatory cells, but distinct in quantitative terms. TLR-4 positive cells were the most frequent. A portion of cells expressed both, TLR and HLA-DR. It is of interest that TLRs tested were expressed not only on cells of inflammatory infiltrate, but also on tumor cells. This fact may be an important factor in tumor escape from immune surveillance. It is notable, that both, TLRs and HLA-DR were shown to be co-expressed, what may favor the role and impact of TLRs in antigen presentation. Further studies are needed to elucidate TLRs function in the course of neoplastic process.