The negative prognostic value of TRAIL overexpression in oral squamous cell carcinomas does not preclude the potential therapeutic use of recombinant TRAIL

Squamous cell carcinoma (SCC) of the head and neck is a common malignancy accounting for over 300,000 cases worldwide every year [1] and occurring at all ages including in children [2]. Of all malignancies locaded in the head and neck region (i.e., oral cavity, pharynx, larynx and paranasal sinuses), the OSCC in its strictest definition (i.e. in front of the tonsils) accounts for the vast majority of cases [1–4]. Surgery remains the first line of treatment for oral cancer, in combination with radiotherapy or chemotherapy [3]. Nevertheless, the poor outcome of many patients affected by OSCC underline the urgent need for innovative therapeutic approaches. In this respect, the development of selective tumor-biology based therapies, that can improve current therapy and allow more tolerable treatment regimens, has become a main field of interest in cancer research. Previous studies have shown that the TNF-family member TRAIL exhibits selective anti-tumor activity due to its unique ability to induce apoptosis in a variety of continuous cancer cell lines and primary tumor cells, displaying minimal or absent toxicity on most normal cells and tissues [5]. Like other members of the TNF family of proteins, TRAIL can be expressed as type II transmembrane protein or as a soluble protein [6] and, besides inducing apoptosis of cancer cells, it plays a variety of biological functions on immune cells and on other cells of hematopoietic origin [6]. There are several ongoing phase I and phase II clinical trials to evaluate the potential anti-cancer activity of soluble recombinant TRAIL in both solid tumors [7] and hematological malignancies [8]. On these bases, the aim of the present study was to investigate the expression of TRAIL in a large sample (n = 134) of paraffin-embedded OSCC specimens and to assess whether this has a prognostic significance for the survival of patients suffering from OSCC. In addition, by using three continuous cell lines (PE15D, PE46 and PE49) of OSCC origin, we analyzed the potential biological significance of the high TRAIL expression in OSCC cells and the response of OSCC cells to treatment in vitro with soluble recombinant TRAIL.