Apoptosis Resistance in Cutaneous T-Cell Lymphoma

The clinical course of cutaneous T-cell lymphomas (CTCL) is slow, possibly suggesting resistance of the tumor cells to apoptosis. In order to better understand this concept, we analyzed the pathways of activation-induced cell death (AICD), both in CTCL-tumor cell lines and in circulating CD4(+) cells from patients with Sezary's syndrome. In our experiments we found no increased expression of c- FLIP, whereas, there was no apoptosis induced by alpha CD3 antibody. The resistance to AICD showing reduced apoptosis after TCR stimulation was found significant, as compared to normal controls. Since the CD95 receptor was found functionally responsive, inhibitory signals interacting with TCR stimulation reduce intracellular ROS and Ca2+ and thereby block the induction of the CD95L, which is required for the induction of AICD. Based on these findings new therapeutic approaches in CTCL may be considered.