Fas ligand expression in thyroid carcinomas: A potential mechanism of immune evasion

Fas ligand (FasL) induces apoptosis by cross-linking the Fas receptor and i s expressed by cells of the immune system. Recently, Fast was found in mali gnant tumors, suggesting that it helps them escape immune surveillance by e liminating infiltrating lymphocytes. We investigated the presence of Fast i mmunohistochemically in 48 thyroid carcinomas and by Western blotting and R T-PCR in 5 thyroid carcinoma cell lines. We found that in contrast to norma l thyroid tissue, Fast was highly expressed in all papillary, follicular, a nd Huerthle carcinomas. Medullary carcinomas lacked or had minimal Fast exp ression. In papillary carcinomas, high levels of expression correlated inde pendently with aggressive histology and unfavorable clinical presentation. Fast was also present in all thyroid cell lines. Thyroid carcinoma cells ki lled Fas-sensitive targets in a FasL-dependent manner in a coculture experi ment. Cross-linking of Fas induced apoptosis in thyroid carcinoma cells onl y in the presence of cycloheximide. We conclude that Fast is specifically e xpressed in thyroid carcinomas of follicular epithelial origin, may help th em evade the immune system, and may have prognostic implications in papilla ry carcinoma, as it is associated with a more aggressive phenotype. Thyroid carcinoma cells avoid Fas-mediated suicide possibly by expressing an inhib itor of the Fas apoptotic pathway.