Papillary thyroid cancer the possible role of death ligands in tumor immunology
Emese Mezosi1, Ferenc Gyory2, Agnes Borbely2, Bernadett Ujhelyi2, Gyorgyike Soos2, Endre V. Nagy2, Zsuzsa Varga2 & Laszlo Bajnok1
Papillary thyroid cancer (PTC) cells and immune cells can kill each other by death ligands. Death ligands induce apoptosis only in sensitive cells. The sensitivity to apoptosis is regulated in a complex and poorly understood manner. The aim of this study was to investigate the Fas ligand (FasL) and Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) expression in PTC cells and tumor infiltrating immune cells. Twenty-six PTCs without and fifteen PTCs with cervical lymph node metastasis were examined by immunohistochemistry. Lymphocytic and macrophage infiltration, HLA-DR, FasL and TRAIL expressions were investigated. The intensity of positive staining was evaluated by a semiquantitative score system. Macrophages and lymphocytes infiltrated the majority of tumor samples. FasL expression of cancer cells was universal and did not show any correlation with the intensity of lymphocytic infiltration and lymph node metastasis. A small subgroup of lymphocytes in close proximity to tumor cells was strongly positive for FasL. Lymphocytes did not express TRAIL. TRAIL expression of tumor cells was increased in PTCs with lymph node metastasis (P=0.01). Macrophages were negative for death ligands. In summary, increased TRAIL expression of tumor cells may inhibit the anti-tumor immunity and promote the formation of lymph node metastasis. A subgroup of lymphocytes can use FasL for tumor cell killing.
This work was supported by a grant from the Hungarian Medical Research Council (ETT 186/2003).