Expression levels of B7-H3 and TLT-2 in human oral squamous cell carcinoma

Abstract

Abstract. The aim of the present study was to investigate the role of immune regulatory molecules B7-H3 [also known as cluster of differentiation 276] and triggering receptor expressed on myeloid cell-like transcript-2 (TLT-2) in patients with oral squamous cell carcinoma (OSCC). Human OSCC samples were obtained from 76 patients (female, 32; male, 44; age range, 23-81 years; median age, 50.9 years) that underwent resection for OSCC at Peking University Shenzhen Hospital (Shenzhen, China) between 2007 and 2010. In addition, control oral mucosal samples were obtained from 76 healthy individuals (female, 36; male, 40; age range, 21-62 years; median age, 45.3 years) during wisdom tooth extraction. Protein and gene expression levels of B7-H3 and TLT-2 were determined by immunohistochemical analysis and reverse transcription-polymerase chain reaction (RT-PCR). In the healthy oral mucosa samples, B7-H3 expression was identified to be weak, while the expression of TLT-2 was only detected sporadically in the cell membrane and cytoplasm. By contrast, the two regulatory molecules were widely expressed in the aforementioned localizations in human OSCC specimens upon immunohistochemical examination. Furthermore, quantitative RT-PCR confirmed the presence of significantly higher B7-H3 and TLT-2 expression levels in OSCC specimens compared with the oral mucosa of healthy individuals. The significantly higher expression levels of B7-H3 and TLT-2 in human OSCC specimens may indicate an inhibitory role of these molecules in the antitumoral immune response. To investigate interactions between these two molecules and individual antitumoral immune response in OSCC patients, prospective clinical studies with an adequate sample size are required. IntroductionThe antitumoral immune response is a complex physiological process involving a variety of immune cells and molecules, including membrane molecules and dissolubility factors (1). As well as the engagement of T cell receptors, costimulation with immune regulatory molecules is required for the optimal activation of T cells (2). The B7 family, a group of costimulatory and coinhibitory proteins, encompasses critical ligands that interact with known and unknown receptors on the surface of T lymphocytes, regulating stimulation or inhibition (3). The aberrant expression of members of the B7 family is considered to be a mechanism by which human malignancies may escape host immune surveillance (3-5).B7-H3 [also known as cluster of differentiation (CD) 276], a member of the B7 family, is expressed on the surface of lymphoid cells, including dendritic cells, monocytes/macrophages and activated T cells. In addition, it is expressed on the surface of non-lymphoid tissue cells, including epithelial, anterior pituitary progenitor and muscle cells, as well as fibroblast-like synoviocytes (3,4). At present, the regulatory role of B7-H3 in tumor immunity remains controversial. A number of studies considered B7-H3 to be a costimulatory molecule promoting T-cell activation and proliferation and, thus,...

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