A) Proposed response of CTCL cells with downregulated/absent expression of death receptors/ligands to conventional ALA-PDT. The generation of ROS by PDT triggers apoptosis via caspase 9 cleavage and activates pathways which are known to upregulate some death receptor ligands. B) Proposed response of CTCL cells to ePDT. The binding of fully functional death receptors with their ligands triggers an additional apoptotic pathway, the extrinsic caspase 8-mediated pathway, which leads to enhanced apoptosis. See discussion for further details.
*DR: death receptor, e.g. FAS, DR4; **DRL: death receptor ligand, e.g. FASL, TRAIL; MTX: methotrexate; ROS: reactive oxygen species; t-BID: truncated BH3 interacting-domain death agonist; JNK: Jun N-terminal kinase.