This study, shiwsthat the levels of TRAIL expression are significantly associated with the clinical outcome of patients with OSCC. In particular, the study shows that OSCC with higher TRAIL expression levels define subgroups of patients with poor prognosis. Interestingly, similar findings have been reported for other types of cancers. High TRAIL expression was significantly associated with poor clinical prognosis in patients with renal cell carcinomas, while it had no prognostic value in patients with stage III colon cancers. Since TRAIL is reported to promote migration, invasion, and metastasis in certain tumor cell types, an increased expression of TRAIL in OSCC cells might represent a biological advantage, at least in some subsets of cases. In addition, it has been shown that TRAIL induces cell cycle arrest in normal T lymphocytes. The immune evasion hypothesis has been previously evoked also to explain the increased expression of TRAIL by other solid tumors. This hypothesis was strengthened by in vitro co-culture experiments in which OSCC efficiently killed the TRAIL-sensitive HL-60 cells in a TRAIL-dependent manner, as demonstrated by the ability of TRAIL-R2-Fc chimera to block the interaction between OSCC transmembrane TRAIL and HL-60 TRAIL-receptors. Interestingly, however, we also found that recombinant soluble TRAIL showed high cytotoxicity when added to OSCC cell lines. In line with our current results, it has been previously reported that treatment with TRAIL, used either alone or in combination with other drugs, resulted in induction of cell death in head and neck squamous cell carcinomas. Taken together, our data clearly indicate that a high expression of TRAIL in OSCC cells, as observed both at immunohistochemistry and at flow cytometry, does not necessarily imply that OSCC cells are resistant to cytotoxicity induced by recombinant soluble TRAIL. Similarly, we previously demonstrated in a mouse model of atherosclerosis that murine macrophages expressing high levels of TRAIL are susceptible to apoptosis induced by the in vivo administration of recombinant TRAIL. These studies suggest that although high levels of tumor TRAIL expression define subgroups of OSCC patients with poor prognosis, the clinical grade formulation of recombinant TRAIL/Apo-2L (Dulanermin) should be further considered for the treatment of OSCC.
The negative prognostic value of TRAIL overexpression in oral squamous cell carcinomas does not preclude the potential therapeutic use of recombinant TRAIL.
CARINCI, Francesco;PALMIERI, Annalisa;MELLONI, Elisabetta;ZAULI, Giorgio;SECCHIERO, Paola
2012
Abstract
This study, shiwsthat the levels of TRAIL expression are significantly associated with the clinical outcome of patients with OSCC. In particular, the study shows that OSCC with higher TRAIL expression levels define subgroups of patients with poor prognosis. Interestingly, similar findings have been reported for other types of cancers. High TRAIL expression was significantly associated with poor clinical prognosis in patients with renal cell carcinomas, while it had no prognostic value in patients with stage III colon cancers. Since TRAIL is reported to promote migration, invasion, and metastasis in certain tumor cell types, an increased expression of TRAIL in OSCC cells might represent a biological advantage, at least in some subsets of cases. In addition, it has been shown that TRAIL induces cell cycle arrest in normal T lymphocytes. The immune evasion hypothesis has been previously evoked also to explain the increased expression of TRAIL by other solid tumors. This hypothesis was strengthened by in vitro co-culture experiments in which OSCC efficiently killed the TRAIL-sensitive HL-60 cells in a TRAIL-dependent manner, as demonstrated by the ability of TRAIL-R2-Fc chimera to block the interaction between OSCC transmembrane TRAIL and HL-60 TRAIL-receptors. Interestingly, however, we also found that recombinant soluble TRAIL showed high cytotoxicity when added to OSCC cell lines. In line with our current results, it has been previously reported that treatment with TRAIL, used either alone or in combination with other drugs, resulted in induction of cell death in head and neck squamous cell carcinomas. Taken together, our data clearly indicate that a high expression of TRAIL in OSCC cells, as observed both at immunohistochemistry and at flow cytometry, does not necessarily imply that OSCC cells are resistant to cytotoxicity induced by recombinant soluble TRAIL. Similarly, we previously demonstrated in a mouse model of atherosclerosis that murine macrophages expressing high levels of TRAIL are susceptible to apoptosis induced by the in vivo administration of recombinant TRAIL. These studies suggest that although high levels of tumor TRAIL expression define subgroups of OSCC patients with poor prognosis, the clinical grade formulation of recombinant TRAIL/Apo-2L (Dulanermin) should be further considered for the treatment of OSCC.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
