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Epigenetically Enhanced PDT Induces Significantly Higher Levels of Multiple Extrinsic Pathway Apoptotic Factors than Standard PDT , Resulting in Greater Extrinsic and Overall Apoptosis of Cutaneous T‐cell Lymphoma
Author(s) -
Salva Katrin A.,
Kim Youn H.,
Rahbar Ziba,
Wood Gary S.
Publication year - 2018
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.12925
Subject(s) - apoptosis , cutaneous t cell lymphoma , photodynamic therapy , cancer research , fas ligand , jurkat cells , lymphoma , uvb induced apoptosis , programmed cell death , immunology , biology , medicine , chemistry , t cell , mycosis fungoides , caspase , immune system , organic chemistry , biochemistry
Aminolevulinate‐based photodynamic therapy ( ALA ‐ PDT ) selectively eliminates diseased tissues primarily through the induction of intrinsic apoptotic pathway. ALA ‐ PDT is a first‐line therapy for actinic keratosis, however, it is less effective for cutaneous T‐cell lymphoma ( CTCL ). We have previously demonstrated that the resistance of CTCL to apoptosis correlates with decreased expression of death receptors such as FAS , and that methotrexate functions as an epigenetic regulator that reestablishes the susceptibility of CTCL to extrinsic pathway apoptosis. We showed previously that MTX augments the effectiveness of PDT by sensitizing cells to apoptosis by induction of apoptotic factors, a process we call “epigenetically enhanced” PDT ( e PDT ). Here, in CTCL cell lines, leukemic CTCL cells, and normal blood T cells, we analyzed multiple components of the FAS , TRAIL , and TNF families using multispectral imaging of immunostained cytopreparations, a quantitative technique with five‐fold greater sensitivity than standard immunocytology. e PDT induced significantly greater FAS , FASL , TRAIL ‐R1 & ‐R2, and TNF α levels than standard PDT . This correlated with significantly greater induction of extrinsic pathway apoptosis and/or overall apoptosis in all CTCL samples. There was no appreciable effect on normal T cells. These data set the stage for clinical trials of e PDT as a novel localized treatment of CTCL.