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TRAIL: a mechanism of tumor surveillance in an immune privileged site
Hae-Ock Lee1, John M Herndon, Ramon Barreiro
1Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Abstract:
TRAIL is a recently described member of the TNF superfamily. The ability of TRAIL to induce apoptosis in a large number of tumors has stimulated interest in TRAIL as a tumor therapeutic agent. Although TRAIL mRNA is expressed in a number of tissues, its functional significance to various organs is unknown. Because tumors rarely develop in the eye, we have examined this organ for functional TRAIL expression. Our analysis revealed that TRAIL mRNA and protein are constitutively expressed on numerous ocular structures, including the cornea and retina. More importantly, ocular tissue displays functional TRAIL as determined by in vitro killing of TRAIL-sensitive tumor cell lines. Previous studies have shown that ocular tissue also expresses functional Fas ligand (FasL). To assess the contribution of TRAIL and FasL for tumor cell killing in the eye, cell lines susceptible to both TRAIL and FasL were examined. The results show that ocular tissue kills via either ligand, suggesting a compensatory mechanism between TRAIL and FasL. Collectively, these results provide physiological evidence for ocular TRAIL expression, and suggest a role for this molecule in tumor surveillance in an immune privileged site.
Insights
The eye expresses functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL), suggesting a compensatory mechanism for tumor surveillance in this immune-privileged site.
Area of Science:
- Immunology
- Ophthalmology
- Molecular Biology
Background:
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a protein with potential as a cancer therapeutic agent.
- The functional significance of TRAIL expression in various organs is not well understood.
- The eye rarely develops tumors, making it an interesting model for studying tumor surveillance.
Purpose of the Study:
- To investigate the expression and function of TRAIL in ocular tissues.
- To determine the role of TRAIL and Fas ligand (FasL) in tumor cell killing within the eye.
- To explore potential compensatory mechanisms between TRAIL and FasL in ocular immune surveillance.
Main Methods:
- Analysis of TRAIL mRNA and protein expression in ocular structures.
- In vitro assays using TRAIL-sensitive tumor cell lines and ocular tissue.
- Examination of tumor cell killing by ocular tissue expressing both TRAIL and FasL.
Main Results:
- TRAIL mRNA and protein are constitutively expressed in ocular structures like the cornea and retina.
- Ocular tissue demonstrated functional TRAIL activity, killing TRAIL-sensitive tumor cell lines.
- Ocular tissue exhibited tumor cell killing via both TRAIL and FasL, indicating a compensatory mechanism.
Conclusions:
- Physiological evidence supports functional TRAIL expression in the eye.
- TRAIL and FasL may act in a compensatory manner for tumor surveillance in the immune-privileged ocular environment.
- This study suggests a novel role for TRAIL in ocular tumor surveillance.
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