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Fas ligand expression in thyroid carcinomas: a potential mechanism of immune evasion
N Mitsiades1, V Poulaki, G Mastorakos
1Laboratory of Pathology, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
Fas ligand (FasL) induces apoptosis by cross-linking the Fas receptor and is expressed by cells of the immune system. Recently, FasL was found in malignant tumors, suggesting that it helps them escape immune surveillance by eliminating infiltrating lymphocytes. We investigated the presence of FasL immunohistochemically in 48 thyroid carcinomas and by Western blotting and RT-PCR in 5 thyroid carcinoma cell lines. We found that in contrast to normal thyroid tissue, FasL was highly expressed in all papillary, follicular, and Huerthle carcinomas. Medullary carcinomas lacked or had minimal FasL expression. In papillary carcinomas, high levels of expression correlated independently with aggressive histology and unfavorable clinical presentation. FasL was also present in all thyroid cell lines. Thyroid carcinoma cells killed Fas-sensitive targets in a FasL-dependent manner in a coculture experiment. Cross-linking of Fas induced apoptosis in thyroid carcinoma cells only in the presence of cycloheximide. We conclude that FasL is specifically expressed in thyroid carcinomas of follicular epithelial origin, may help them evade the immune system, and may have prognostic implications in papillary carcinoma, as it is associated with a more aggressive phenotype. Thyroid carcinoma cells avoid Fas-mediated suicide possibly by expressing an inhibitor of the Fas apoptotic pathway.
Insights
Fas ligand (FasL) is highly expressed in most thyroid carcinomas, potentially helping tumors evade immune detection. This expression may indicate a more aggressive cancer in papillary types.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Fas ligand (FasL) induces apoptosis and is expressed by immune cells.
- FasL in tumors suggests a mechanism for immune evasion by eliminating lymphocytes.
- The role of FasL in thyroid cancer pathogenesis and immune surveillance is unclear.
Purpose of the Study:
- To investigate the expression and role of FasL in various types of thyroid carcinoma.
- To determine if FasL expression correlates with clinicopathological features and prognosis in thyroid cancer.
- To assess the functional significance of FasL in thyroid cancer cell lines.
Main Methods:
- Immunohistochemistry was used to detect FasL in 48 thyroid carcinoma samples.
- Western blotting and RT-PCR analyzed FasL expression in 5 thyroid carcinoma cell lines.
- Coculture experiments assessed the cytotoxic effect of thyroid carcinoma cells on Fas-sensitive targets.
Main Results:
- FasL was highly expressed in papillary, follicular, and Huerthle cell carcinomas, but minimally in medullary carcinomas.
- High FasL expression in papillary carcinomas correlated with aggressive histology and unfavorable clinical presentation.
- Thyroid carcinoma cells demonstrated FasL-dependent killing of Fas-sensitive targets and resisted Fas-mediated apoptosis without cycloheximide.
Conclusions:
- FasL is specifically expressed in thyroid carcinomas of follicular epithelial origin.
- FasL expression may contribute to immune evasion in thyroid cancer.
- FasL has potential prognostic implications in papillary thyroid carcinoma, associated with a more aggressive phenotype.