Inverse relation of Fas-ligand and tumor-infiltrating lymphocytes in angiosarcoma - Indications of apoptotic tumor counterattack

Fas and Fas-L regulate immune responses through the induction of cell death . Fas-L is commonly expressed in activated immune cells and in the endothel ium. In the latter it contributes to the inhibition of transvascular cell m igration by the induction of apoptosis in Fas-bearing lymphocytes. Here we investigated whether the Fas/Fas-L system may regulate lymphocyte invasion into angiosarcomas. Fas and Fas-L expression was quantitatively determined in different grade angiosarcomas (n = 40) and related to the number of extr avasated tumor-infiltrating lymphocytes (TILs). Fas expression was detected in <50% of the cases. in positive tumors both the number of Fas-positive c ells and the staining intensity were highly variable and did not correlate with the number of TILs, the mean time of survival, and the histopathologic al tumor grade. By contrast, Fas-L expression was detected in >70% of the c ases and the relative numbers of Fas-L-positive cells correlated inversely with the numbers of CD3- and CD8-positive TILs (P less than or equal to0.00 4). The survival times of patients with high Fas-L-expressing angiosarcomas were significantly reduced as compared to patients with low Fas-L-expressi ng tumors. Our results show that angiosarcomas with low Fas-L expression ar e characterized by numerous TILs, whereas sarcomas with high Fas-L expressi on show significantly reduced numbers of TILs. These results suggest that t he Fas/Fas-L system may repress TIL invasion into angiosarcoma and by this may contribute to the evasion of the anti-tumor immune surveillance of angi osarcoma in the course of an apoptotic tumor counterattack mechanism.